TY - JOUR
AU - Doble, Mukesh
AB - Abstract Mannosylerythritol lipids (MELs) are surface active compounds that belong to the glycolipid class of biosurfactants (BSs). MELs are produced by Pseudozyma sp. as a major component while Ustilago sp. produces them as a minor component. Although MELs have been known for over five decades, they recently regained attention due to their environmental compatibility, mild production conditions, structural diversity, self-assembling properties and versatile biochemical functions. In this review, the MEL producing microorganisms, the production conditions, their applications, their diverse structures and self-assembling properties are discussed. The biosynthetic pathways and the regulatory mechanisms involved in the production of MEL are also explained here. Introduction Biosurfactants (BSs) or microbial surface active compounds are of recent interest due to their unique properties including structural diversity, higher biodegradability, lower toxicity, higher foaming ability, higher selectivity and specific activity at extreme conditions (pH, temperature and ionic strength) and mild production conditions when compared to the chemical surfactants. BSs are amphiphilic molecules with polar and non-polar domains [6, 13, 42, 53, 59]. There are five main classes of BSs, namely lipopeptides; glycolipids; fatty acids including neutral lipids and phospholipids; polymeric and particulate [6, 13, 53, 59]. Among these, the first two classes show wide range of applications in food, cosmetics, and pharmaceutical industries [3, 6, 57, 61, 62]. They are used in removing soil contaminants including heavy metals, oils and other toxic pollutants [13, 52, 53, 61]. Some of the BSs are potential antimicrobial agents and are suitable alternatives to synthetic antibiotics [3, 38, 57, 62]. Except for a few, the physiological roles of BSs in general are not yet completely characterized. BSs are essential for the motility (swarming and gliding) of the microorganisms. For example, surfactin production and flagellar biosynthesis are crucial for swarming motility in B. subtilis [13, 30]. Similarly, Serratia marcescens depends on serrawettin for surface locomotion and access to water repelling surfaces [13, 47]. 3-(3-Hydroxyalkanoyloxy) alkanoic acid (HAA), the intermediate in the rhamnolipid biosynthesis pathway, plays an essential role in swarming motility [7, 13]. BSs regulate the attachment and detachment of the microorganisms to or from solid substrates [13, 53, 58]. Rhamnolipids are essential to maintain the architecture of the biofilm [4, 13] and are considered as one of the virulence factors in Pseudomonas sp. [4, 13, 58]. Rhamnolipids, mannosylerythritol lipid and surfactin are a few examples of BSs showing antimicrobial and antibiotic properties. Thus they confer a competitive advantage to the organism during colonization and cell–cell competition [13, 58]. BSs enhance the accessibility of hydrocarbon substrates by forming small emulsion droplets and increase the surface area of the insoluble substrates [13, 53, 58]. BSs form complex (chelate) with heavy metals including Cd2+, Pb2+, Zn2+ and Hg2+ and hence reduce their toxicity [13, 52, 58]. They act as carbon and energy storage molecules and remain as a protective layer for the microorganisms against the environment with high ionic strength [41, 42, 58]. BSs may be the byproducts released in response to the environmental changes and may have a role in DNA transfer in natural environment, since they can enhance gene uptake via transfection [13, 23, 24, 58, 61]. Biosurfactant containing 4-O-β-d-mannopyranosyl-meso-erythritol as the hydrophilic group and a fatty acid and/or an acetyl group as the hydrophobic moiety is known as mannosylerythritol lipid (MEL) (Fig. 1) [43]. MEL is reported to be secreted by Ustilago sp. (as a minor component along with cellobiose lipid (CL)) [14], Schizonella melanogramma (shizonellin) [5], and Pseudozyma sp. (as a major component) [33]. Since the synthesis of MEL is not growth associated, it can also be produced by using resting (stationary phase) cells of yeast. MEL acts as an energy storage material in the yeast cells similar to triacylglycerols [42]. MELs are shown to reduce the surface tension of water to less than 30 mN m−1 [32, 37, 42, 45]. Even though BSs have a wide range of applications, in general, they are not yet commercially viable mainly due to their low yield leading to high production cost. However, MEL (165 g/L) and sophorolipid (above 400 g/L) are produced in high quantity [42] and hence may become economically attractive. Fig. 1 Open in new tabDownload slide Structure of MEL [43] (MEL-A: R1 = R2 = Ac; MEL-B: R1 = Ac, R2 = H; MEL-C: R1 = H, R2 = Ac: n = 6–10) MEL: why? The increasing interest in MELs could be attributed to their pharmaceutical applications [60, 73] and versatile biochemical functions including antitumor and differentiation inducing activities against human leukemia cells, rat peochromocytoma cells and mouse melanoma cells [25–27, 68, 71–73]. They can be used in the treatment of schizophrenia or diseases caused by dopamine metabolic dysfunction [67, 72] and microbial infections [37]. MELs are used in the purification of lectins (Immunoglobulin G) [9, 15, 16, 21, 39] and in the preparation of ice-slurry as an anti-agglomeration agent [41, 42]. Self-assembling properties [17–20, 39, 43, 70] of MELs are of recent interest because this behavior could be leveraged in gene transfection and drug delivery [23, 24, 42, 43, 65, 66]. The increasing number of novel MEL producers, their proven structural diversity, their self-assembling properties and myriad applications are discussed in this review. Structural diversity of MEL and its microbial sources MELs are secreted by several microorganisms and they are first noted as oily compounds in the cultured suspension of Ustilago maydis PRL-627 by Haskins et al. [14]. This microorganism was shown to produce MEL along with CL when glucose was used as the carbon source [2, 8, 14]. Bhatttacharjee et al. [1] characterized MEL as a glycolipid, especially as a mixture of partially acylated derivative of 4-O-β-d-mannopyranosyl-d-erythritol, containing C2:0, C12:0, C14:0, C14:1, C16:0, C16:1, C18:0 and C18:1 fatty acids as the hydrophobic groups. Schizonella melanogramma was the second microorganism identified as a MEL producer (schizonellin), but not in association with CL [5]. Table 1 summarizes the structural variants of the MELs and the corresponding microbial sources. These variants arise due to the following reasons: Structural variants of MEL and their corresponding microbial sources Microorganism . Sugar . Fatty acid profile . Type of MEL (major component) . References . Ustilago nuda PRL-627 4-O-β-d-mannopyranosyl-d-erythritol C2:0, C12:0, C14:0, C14:1, C16:0, C16:1, C18:0, and C18:1 NA [1] Candida (Pseudozyma) sp. B7 4-O-β-d-mannopyranosyl-d-erythritol C7–C14 MEL-B7 [29] Pseudozyma antarctica T-34 4-O-β-d-mannopyranosyl-erythritol C8:0 (27.26%), C10:0 (21.28%), C10:1 (27.22%) MEL-A and MEL-B (it produce all four types) [34, 40] Ustilago maydis DSM 4500 and ATCC 1482 4-O-β-d-mannopyranosyl-d-erythritol C14:1 (43%), C6:0 (20%) and C16:1 (12%) MEL-A [63] Schizonella melanogramma 4-O-β-d-mannopyranosyl-d-erythritol C14:0, C16:1, C16:0, C18:0, C18:1 Schizonellin A and schizonellin B (similar to MEL-A and -B) [5] Kurtzmanomyces sp. I-11 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (36.4%), C12:0 (11.9%), C14:2 (25.9%) MEL-I-11 [28] Candida sp. SY16 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6:0, C12:0, C14:0, and C14:1 MEL-A [31] Pseudozyma aphidis DSM 70725 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C10:0, C10:1, and C8:0 MEL-A [54] Pseudozyma rugulosa NBRC 10877 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (28.09%), C10:0 (21.68%), C10:1 (22.94%) MEL-A [48] Pseudozyma hubeiensis KM-59 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6, C12 and C16 MEL-C (65%) [45, 46] Pseudozyma shaxiensis 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C16:0, C16:1, C16:2, and C14:1 MEL-C [10] P. tsukubaensis JCM 10324T 1-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8, C12, C14 MEL-B with new diastereomer of sugar [12, 49] P. fusiformata 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6 and C8 MEL-A [49] Pseudozyma graminicola CBS 10092 4-O-β-d-mannopyranosyl-(1→ 4)-D-meso-erythritol C6:0, C8:0, C12:0, C12:1, C14:0, and C14:1 MEL-C (85%) [50] P. antarctica and P. parantarctica 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0, C10:0, C12:0, C14:0, C14:1 Monoacylated MEL [11] P. antarctica and P. rugulosa 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C18:1, C18:0, C10:0, C10:1, C16:0, and C8:0 Triacylated MEL [44] P. siamensis CBS 9960 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C14:2, C16:0, C16:1, C16:2 (C2 or C4) at the C-2′ position and (C16) at the C-3′ position of the mannose moiety MEL-C mixture of monoacetylation and diacetylation [57] Microorganism . Sugar . Fatty acid profile . Type of MEL (major component) . References . Ustilago nuda PRL-627 4-O-β-d-mannopyranosyl-d-erythritol C2:0, C12:0, C14:0, C14:1, C16:0, C16:1, C18:0, and C18:1 NA [1] Candida (Pseudozyma) sp. B7 4-O-β-d-mannopyranosyl-d-erythritol C7–C14 MEL-B7 [29] Pseudozyma antarctica T-34 4-O-β-d-mannopyranosyl-erythritol C8:0 (27.26%), C10:0 (21.28%), C10:1 (27.22%) MEL-A and MEL-B (it produce all four types) [34, 40] Ustilago maydis DSM 4500 and ATCC 1482 4-O-β-d-mannopyranosyl-d-erythritol C14:1 (43%), C6:0 (20%) and C16:1 (12%) MEL-A [63] Schizonella melanogramma 4-O-β-d-mannopyranosyl-d-erythritol C14:0, C16:1, C16:0, C18:0, C18:1 Schizonellin A and schizonellin B (similar to MEL-A and -B) [5] Kurtzmanomyces sp. I-11 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (36.4%), C12:0 (11.9%), C14:2 (25.9%) MEL-I-11 [28] Candida sp. SY16 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6:0, C12:0, C14:0, and C14:1 MEL-A [31] Pseudozyma aphidis DSM 70725 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C10:0, C10:1, and C8:0 MEL-A [54] Pseudozyma rugulosa NBRC 10877 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (28.09%), C10:0 (21.68%), C10:1 (22.94%) MEL-A [48] Pseudozyma hubeiensis KM-59 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6, C12 and C16 MEL-C (65%) [45, 46] Pseudozyma shaxiensis 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C16:0, C16:1, C16:2, and C14:1 MEL-C [10] P. tsukubaensis JCM 10324T 1-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8, C12, C14 MEL-B with new diastereomer of sugar [12, 49] P. fusiformata 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6 and C8 MEL-A [49] Pseudozyma graminicola CBS 10092 4-O-β-d-mannopyranosyl-(1→ 4)-D-meso-erythritol C6:0, C8:0, C12:0, C12:1, C14:0, and C14:1 MEL-C (85%) [50] P. antarctica and P. parantarctica 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0, C10:0, C12:0, C14:0, C14:1 Monoacylated MEL [11] P. antarctica and P. rugulosa 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C18:1, C18:0, C10:0, C10:1, C16:0, and C8:0 Triacylated MEL [44] P. siamensis CBS 9960 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C14:2, C16:0, C16:1, C16:2 (C2 or C4) at the C-2′ position and (C16) at the C-3′ position of the mannose moiety MEL-C mixture of monoacetylation and diacetylation [57] NA not available Open in new tab Structural variants of MEL and their corresponding microbial sources Microorganism . Sugar . Fatty acid profile . Type of MEL (major component) . References . Ustilago nuda PRL-627 4-O-β-d-mannopyranosyl-d-erythritol C2:0, C12:0, C14:0, C14:1, C16:0, C16:1, C18:0, and C18:1 NA [1] Candida (Pseudozyma) sp. B7 4-O-β-d-mannopyranosyl-d-erythritol C7–C14 MEL-B7 [29] Pseudozyma antarctica T-34 4-O-β-d-mannopyranosyl-erythritol C8:0 (27.26%), C10:0 (21.28%), C10:1 (27.22%) MEL-A and MEL-B (it produce all four types) [34, 40] Ustilago maydis DSM 4500 and ATCC 1482 4-O-β-d-mannopyranosyl-d-erythritol C14:1 (43%), C6:0 (20%) and C16:1 (12%) MEL-A [63] Schizonella melanogramma 4-O-β-d-mannopyranosyl-d-erythritol C14:0, C16:1, C16:0, C18:0, C18:1 Schizonellin A and schizonellin B (similar to MEL-A and -B) [5] Kurtzmanomyces sp. I-11 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (36.4%), C12:0 (11.9%), C14:2 (25.9%) MEL-I-11 [28] Candida sp. SY16 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6:0, C12:0, C14:0, and C14:1 MEL-A [31] Pseudozyma aphidis DSM 70725 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C10:0, C10:1, and C8:0 MEL-A [54] Pseudozyma rugulosa NBRC 10877 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (28.09%), C10:0 (21.68%), C10:1 (22.94%) MEL-A [48] Pseudozyma hubeiensis KM-59 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6, C12 and C16 MEL-C (65%) [45, 46] Pseudozyma shaxiensis 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C16:0, C16:1, C16:2, and C14:1 MEL-C [10] P. tsukubaensis JCM 10324T 1-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8, C12, C14 MEL-B with new diastereomer of sugar [12, 49] P. fusiformata 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6 and C8 MEL-A [49] Pseudozyma graminicola CBS 10092 4-O-β-d-mannopyranosyl-(1→ 4)-D-meso-erythritol C6:0, C8:0, C12:0, C12:1, C14:0, and C14:1 MEL-C (85%) [50] P. antarctica and P. parantarctica 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0, C10:0, C12:0, C14:0, C14:1 Monoacylated MEL [11] P. antarctica and P. rugulosa 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C18:1, C18:0, C10:0, C10:1, C16:0, and C8:0 Triacylated MEL [44] P. siamensis CBS 9960 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C14:2, C16:0, C16:1, C16:2 (C2 or C4) at the C-2′ position and (C16) at the C-3′ position of the mannose moiety MEL-C mixture of monoacetylation and diacetylation [57] Microorganism . Sugar . Fatty acid profile . Type of MEL (major component) . References . Ustilago nuda PRL-627 4-O-β-d-mannopyranosyl-d-erythritol C2:0, C12:0, C14:0, C14:1, C16:0, C16:1, C18:0, and C18:1 NA [1] Candida (Pseudozyma) sp. B7 4-O-β-d-mannopyranosyl-d-erythritol C7–C14 MEL-B7 [29] Pseudozyma antarctica T-34 4-O-β-d-mannopyranosyl-erythritol C8:0 (27.26%), C10:0 (21.28%), C10:1 (27.22%) MEL-A and MEL-B (it produce all four types) [34, 40] Ustilago maydis DSM 4500 and ATCC 1482 4-O-β-d-mannopyranosyl-d-erythritol C14:1 (43%), C6:0 (20%) and C16:1 (12%) MEL-A [63] Schizonella melanogramma 4-O-β-d-mannopyranosyl-d-erythritol C14:0, C16:1, C16:0, C18:0, C18:1 Schizonellin A and schizonellin B (similar to MEL-A and -B) [5] Kurtzmanomyces sp. I-11 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (36.4%), C12:0 (11.9%), C14:2 (25.9%) MEL-I-11 [28] Candida sp. SY16 6-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6:0, C12:0, C14:0, and C14:1 MEL-A [31] Pseudozyma aphidis DSM 70725 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C10:0, C10:1, and C8:0 MEL-A [54] Pseudozyma rugulosa NBRC 10877 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0 (28.09%), C10:0 (21.68%), C10:1 (22.94%) MEL-A [48] Pseudozyma hubeiensis KM-59 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6, C12 and C16 MEL-C (65%) [45, 46] Pseudozyma shaxiensis 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C16:0, C16:1, C16:2, and C14:1 MEL-C [10] P. tsukubaensis JCM 10324T 1-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8, C12, C14 MEL-B with new diastereomer of sugar [12, 49] P. fusiformata 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C6 and C8 MEL-A [49] Pseudozyma graminicola CBS 10092 4-O-β-d-mannopyranosyl-(1→ 4)-D-meso-erythritol C6:0, C8:0, C12:0, C12:1, C14:0, and C14:1 MEL-C (85%) [50] P. antarctica and P. parantarctica 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C8:0, C10:0, C12:0, C14:0, C14:1 Monoacylated MEL [11] P. antarctica and P. rugulosa 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C18:1, C18:0, C10:0, C10:1, C16:0, and C8:0 Triacylated MEL [44] P. siamensis CBS 9960 4-O-β-d-mannopyranosyl-(1 → 4)-d-meso-erythritol C14:2, C16:0, C16:1, C16:2 (C2 or C4) at the C-2′ position and (C16) at the C-3′ position of the mannose moiety MEL-C mixture of monoacetylation and diacetylation [57] NA not available Open in new tab Number and position of the acetyl group on mannose or erythritol or both. Number of acylation in mannose. Fatty acid chain length and their saturation. The acyl residues in MEL ranged from C7 to C14 and their proportions varied depending upon the carbon source used. For example, Candida sp. B-7 (currently known as Pseudozyma antarctica) produced 4-O-(2′, 6′-di-O-acyl-β-d-mannopyranosyl)-d-erythritol with high yield (25–36 g/L), when it was grown on n-alkane or triglycerides at 30 °C for 7 days but not with carbohydrate as the carbon source [29]. Based on the degree of acetylation at C4 and C6 position, and their order of appearance on the thin layer chromatography (TLC), the MELs (from P. aphidis) are classified as MEL-A, -B, -C and -D. MEL-A representing the diacetylated compound while MEL-B and MEL-C are monoacetylated at C6 and C4, respectively. The completely deacetylated structure is known as MEL-D [54]. Mixtures of these four MELs but predominantly MEL-A and MEL-B were isolated from Candida antarctica strain T34 [33]. Excellent surface active and antimicrobial properties of MELs isolated from T-34 were reported by Kitamoto et al. [37]. Kurtzmanomyces sp. I-11 produces a novel MEL composed of a sugar moiety, 6-O-β-d-mannopyranosyl-(1 → 4)-O-meso-erythritol and a mixture of fatty acids [C8:0 (36.4%), C12:0 (11.9%) and C14:2 (25.9)] [28] as the lipophylic group. Candida antarctica KCTC 7804 which was isolated from an oil contaminated site, produced a MEL containing 6-O-acetyl-2, 3-di-O-alkanoyl-β-d-mannopyranosyl-(1 → 4)-O-meso-erythritol. The lipophilic group of this MEL is a mixture of hexanoic, dodecanoic, tetradecanoic and tetradecenoic fatty acids. The acetyl group is linked at the C-6 position of the d-mannose [31]. Pseudozyma rugulosa NBRC 10877 is reported to produce from soybean oil a mixture of MEL-A (68%), MEL-B (12%) and MEL-C (20%) consisting of C8 and C10 fatty acids as the hydrophobic moiety [48]. P. fusiformata, P. parantarctica and P. tsukubaensis are identified as MEL producers and of these three strains; P. parantarctica produces the highest quantity of MEL (30 g/L). Interestingly, P. parantarctica and P. fusiformata produce mainly MEL-A, whereas P. tsukubaensis produces MEL-B. The strains of Pseudozyma are classified into four groups such as, the first group produces largely MEL; the second produces both MEL and other biosurfactants; the third produces mainly MEL-B; and the fourth produces non-MEL BS [49]. Hence the production of MEL can be used as an important taxonomic index to identify Pseudozyma yeasts [10, 49–51]. MEL-C is produced by Pseudozyma hubeiensis and the major fatty acids in it are C6, C12, and C16 which are different from those of the other MELs reported so far [45]. P. shanxiensis produces a hydrophilic MEL consisting of a mixture of 4-O-[(2′,4′-di-O-acetyl-3′-O-alka(e)noyl)-β-d-mannopyranosyl]-d-erythritol (Fig. 2) and 4-O-[(4′-O-acetyl-3′-O-alka(e)noyl-2′-O-butanoyl)-β-d-mannopyranosyl]-d-erythritol (Fig. 3) and this has much shorter chain (C2 or C4) at the C-2′ position of the mannose moiety compared to other classes of MELs which comprise of a medium chain length acid (C8 to C14) at the C-2′ position [10, 51]. Pseudozyma siamensis CBS 9960 is found to accumulate higher amounts of glycolipid than its closely related species, P. shanxiensis, which is a known MEL-C producer. The former produces a mixture of different types of MEL-C, namely (>84% of the total) 4-O-[(2′,4′-di-O-acetyl-3′-O-alka(e)noyl)-β-d-mannopyranosyl]-d-erythritol and 4-O-[(4′-O-acetyl-3′-O-alka(e)noyl-2′-O-butanoyl)-β-d-mannopyranosyl]-d-erythritol. This MEL-C possess a short-chain length acid (C2 or C4) at the C-2′ position and a long-chain length acid (C16) at the C-3′ position of the mannose moiety, and thus, the hydrophobic part is considerably different from that of conventional MELs, which have two medium-chain length acids (C10) at the C-2′ and C-3′ positions [51]. P. antarctica and P. rugulosa with soybean oil as the carbon source produce the most hydrophobic triacylated MEL namely 1-O-alka(e)noyl-4-O-[(4′,6′-di-O-acetyl-2′,3′-di-O-alka(e)noyl)-β-d-mannopyranosyl]-d-erythritol (Fig. 4) [9]. P. antarctica T-34 produces a hydrophilic monoacylated MEL, 4-O-(3′-O-alka(e)noyl-β-d-mannopyranosyl)-d-erythritol (Fig. 5), with glucose as the carbon source. This MEL reduces the surface tension of water to 33.8 mN/m at a critical micelle concentration (CMC) of 3.6 × 10−4 M, and it has a hydrophilic–lipophilic balance of 12.15. This CMC is 100-fold higher than that of the other MELs reported [11]. A strain of P. hubeiensis KM-59 produces a hydrophilic MEL-C namely (4-O-[4′-O-acetyl-2′,3′-di-O-alka(e)noyl-β-d-mannopyranosyl]-d-erythritol) [46]. Pseudozyma graminicola CBS 10092 also produces MEL-C. It has C6, C8 and C14 acids and is considerably different from the other MEL-C producing Pseudozyma strains such as P. antarctica and P. shanxiensis [50]. Fig. 2 Open in new tabDownload slide Structure of 4-O-[(2′,4′-di-O-acetyl-3′-O-alka(e)noyl)-β-d-mannopyranosyl]-d-erythritol; R2 = Ac; n = 12–16 Fig. 3 Open in new tabDownload slide Structure of 4-O-[(4′-O-acetyl-3′-O-alka(e)noyl-2′-O-butanoyl)-β-d-mannopyranosyl]-d-erythritol; R2 = Ac; n = 12–16 Fig. 4 Open in new tabDownload slide Structure of triacylated MEL; n = 6–10; m = 6–16 Fig. 5 Open in new tabDownload slide Structure of monoacylated MEL; n = 4–14 Pseudozyma tsukubaensis also produces an unusually different carbohydrate structure namely, 1-O-β-(2′,3′-di-O-alka(e)noyl-6′-O-acetyl-d-mannopyranosyl)-d-erythritol (Fig. 6). The configuration of this erythritol moiety in this MEL is opposite to that of the known MEL-B or to other MELs reported [12]. Table 2 summarizes the surface activities of various homologs of MEL. Fig. 6 Open in new tabDownload slide Diastereomer of MEL-B from P. tsukubaensis; n = 6–12 Structural variants of MEL and their surface activities Type of MEL . Critical micelle concentration (M) . Surface tension (mN/m) . Interfacial tension (mN/m) . References . MEL-A 2.7 × 10−6 28.4 2.1 [37] MEL-B 4.5 × 10−6 28.2 2.4 [37] MEL-C (from P. hubeiensis KM-59) 6.0 × 10−6 25.1 – [46] MEL-C (from P. graminicola CBS 10092) 4.0 × 10−6 24.2 – [50] MEL-C (from P. siamensis CBS 9960) 4.5 × 10−6 30.7 – [57] Monoacylated MEL 3.6 × 10−4 33.8 – [11] Type of MEL . Critical micelle concentration (M) . Surface tension (mN/m) . Interfacial tension (mN/m) . References . MEL-A 2.7 × 10−6 28.4 2.1 [37] MEL-B 4.5 × 10−6 28.2 2.4 [37] MEL-C (from P. hubeiensis KM-59) 6.0 × 10−6 25.1 – [46] MEL-C (from P. graminicola CBS 10092) 4.0 × 10−6 24.2 – [50] MEL-C (from P. siamensis CBS 9960) 4.5 × 10−6 30.7 – [57] Monoacylated MEL 3.6 × 10−4 33.8 – [11] Open in new tab Structural variants of MEL and their surface activities Type of MEL . Critical micelle concentration (M) . Surface tension (mN/m) . Interfacial tension (mN/m) . References . MEL-A 2.7 × 10−6 28.4 2.1 [37] MEL-B 4.5 × 10−6 28.2 2.4 [37] MEL-C (from P. hubeiensis KM-59) 6.0 × 10−6 25.1 – [46] MEL-C (from P. graminicola CBS 10092) 4.0 × 10−6 24.2 – [50] MEL-C (from P. siamensis CBS 9960) 4.5 × 10−6 30.7 – [57] Monoacylated MEL 3.6 × 10−4 33.8 – [11] Type of MEL . Critical micelle concentration (M) . Surface tension (mN/m) . Interfacial tension (mN/m) . References . MEL-A 2.7 × 10−6 28.4 2.1 [37] MEL-B 4.5 × 10−6 28.2 2.4 [37] MEL-C (from P. hubeiensis KM-59) 6.0 × 10−6 25.1 – [46] MEL-C (from P. graminicola CBS 10092) 4.0 × 10−6 24.2 – [50] MEL-C (from P. siamensis CBS 9960) 4.5 × 10−6 30.7 – [57] Monoacylated MEL 3.6 × 10−4 33.8 – [11] Open in new tab Microbial production condition The production of MEL in shake flask is reported while very few attempts have been made to produce it in a fermentor. Seed cultures are prepared by inoculating cells grown on slants into test tubes containing a growth medium [4% glucose, 0.3% NaNO3, 0.03% MgSO4, 0.03% KH2PO4, 0.1% yeast extract (pH 6.0)] at 25 °C on a reciprocal shaker (150 rpm) for 2 days [10, 33, 34, 56]. Exactly 1 mL of the seed culture is transferred to a 300 mL Erlenmeyer flask containing 30 mL of the basal medium [4% olive oil, 0.3% NaNO3, 0.03% MgSO4, 0.03% KH2PO4, 0.1% yeast extract (pH 6.0)], which is then incubated on a rotary shaker (220 rpm) at 28 °C for 7 days. Isolation of glycolipid is carried out by solvent extraction. Equal volumes of ethyl acetate and culture medium are mixed together and are allowed to separate in a separating funnel. Solvent layer is collected and evaporated. This fraction is analyzed using TLC on silica plates (Silica gel 60F; Wako) with a solvent system consisting of chloroform/methanol/7 N ammonia solution (65:15:2, by vol). The compounds on the plates are located by charring them at 110 °C for 5 min after spraying a mixture of anthrone and sulfuric acid [10, 34, 56]. The concentrated glycolipids are dissolved in chloroform and then purified by silica gel (Wako-gel C-200) column chromatography using a gradient elution technique with chloroform–acetone (10:0–0:10, vol/vol) solvent mixtures [10, 56]. Table 3 summarizes the production conditions and the corresponding yield in the preparation of MEL by Pseudozyma sp. Effect of the culture conditions and carbon source on the production and composition of MEL by Pseudozyma sp. Type of MEL . Yield (g/L) . Conditions . References . MEL-B7 30 n-Alkane or vegetable oils; batch culture [29] Mixture of MEL-A, -B and -C 47 Soybean oil and resting cells; batch culture [35] Mixture of MEL-A, -B, -C and D 40 Vegetable oils, yeast extract and batch culture [34] 30 Sunflower oil; batch culture [34] Mixture of MEL-A, -B and -C 140 Octadecane; batch culture [40, 42] Mixture of MEL-A, -B, and -C 165 Soybean oil and fed batch reactor [55] Mixture of MEL homologs 95 Glucose:soybean oil (1:1) and intermittent addition of soybean—fed batch culture [32] MEL-B 25 Soybean oil batch culture [12, 45] MEL-C 15 Soybean oil batch culture [45] MEL-C 76.3 Soybean oil and fed batch reactor [46] Type of MEL . Yield (g/L) . Conditions . References . MEL-B7 30 n-Alkane or vegetable oils; batch culture [29] Mixture of MEL-A, -B and -C 47 Soybean oil and resting cells; batch culture [35] Mixture of MEL-A, -B, -C and D 40 Vegetable oils, yeast extract and batch culture [34] 30 Sunflower oil; batch culture [34] Mixture of MEL-A, -B and -C 140 Octadecane; batch culture [40, 42] Mixture of MEL-A, -B, and -C 165 Soybean oil and fed batch reactor [55] Mixture of MEL homologs 95 Glucose:soybean oil (1:1) and intermittent addition of soybean—fed batch culture [32] MEL-B 25 Soybean oil batch culture [12, 45] MEL-C 15 Soybean oil batch culture [45] MEL-C 76.3 Soybean oil and fed batch reactor [46] Open in new tab Effect of the culture conditions and carbon source on the production and composition of MEL by Pseudozyma sp. Type of MEL . Yield (g/L) . Conditions . References . MEL-B7 30 n-Alkane or vegetable oils; batch culture [29] Mixture of MEL-A, -B and -C 47 Soybean oil and resting cells; batch culture [35] Mixture of MEL-A, -B, -C and D 40 Vegetable oils, yeast extract and batch culture [34] 30 Sunflower oil; batch culture [34] Mixture of MEL-A, -B and -C 140 Octadecane; batch culture [40, 42] Mixture of MEL-A, -B, and -C 165 Soybean oil and fed batch reactor [55] Mixture of MEL homologs 95 Glucose:soybean oil (1:1) and intermittent addition of soybean—fed batch culture [32] MEL-B 25 Soybean oil batch culture [12, 45] MEL-C 15 Soybean oil batch culture [45] MEL-C 76.3 Soybean oil and fed batch reactor [46] Type of MEL . Yield (g/L) . Conditions . References . MEL-B7 30 n-Alkane or vegetable oils; batch culture [29] Mixture of MEL-A, -B and -C 47 Soybean oil and resting cells; batch culture [35] Mixture of MEL-A, -B, -C and D 40 Vegetable oils, yeast extract and batch culture [34] 30 Sunflower oil; batch culture [34] Mixture of MEL-A, -B and -C 140 Octadecane; batch culture [40, 42] Mixture of MEL-A, -B, and -C 165 Soybean oil and fed batch reactor [55] Mixture of MEL homologs 95 Glucose:soybean oil (1:1) and intermittent addition of soybean—fed batch culture [32] MEL-B 25 Soybean oil batch culture [12, 45] MEL-C 15 Soybean oil batch culture [45] MEL-C 76.3 Soybean oil and fed batch reactor [46] Open in new tab Rau et al. [56] reported the production of MEL in a bioreactor and the various downstream processing strategies for its recovery and purification. Solvent extraction, adsorption on different types of Amberlite XAD followed by solvent extraction and heating the culture suspension to 110 °C for 10 min were the three downstream methods reported. The last method gave the highest yield of 93 wt% with a purity of 87 wt%, whereas the solvent extraction method gave only 79 wt% yield with 100 wt% purity [56]. Biosynthetic pathway of MEL Kitamoto et al. [37, 43] attempted to relate the substrate and the corresponding product structures. When fatty alcohols or acids of chain length of Cn were used, the products formed were with the chain length of Cn−2, Cn−4, Cn−6, etc. [36, 42]. The authors concluded that the products were the β-oxidation intermediates of the substrates supplied. 2-Bromooctanoic acid [38, 42] (strong inhibitor of the fatty acid β-oxidation) inhibited the production of MEL and the degree of inhibition increased with the increase in the chain length of the substrate supplied. The cerulenin (strong inhibitor to de novo fatty acid synthesis) did not affect the fatty acid composition of MEL. In general, once the fatty acid entered the β-oxidation pathway, it was completely oxidized to an acetyl CoA and the intermediates did not leak out from this cycle [42, 64]. Two types of β-oxidation cycles are present in mammals, namely peroxisomal partial β-oxidation and mitochondrial complete β-oxidation. The former is responsible for the shortening of long and very long chain fatty acids which are then converted into acetyl CoA in the latter cycle [42, 69]. The biosynthetic “chain shortening” pathway of MEL is different from the three generally known pathways in microorganisms, namely, de novo synthesis, chain elongation and intact incorporation [42]. Self-assembling properties of MEL Self-assembly (SA) can be defined as the spontaneous and reversible organization of molecular units into ordered structures by non-covalent interactions without the application of external force or stimulus. Any amphiphilic molecule possesses this ability. For example, ionic and nonionic surfactants at high concentrations can self-assemble into three-dimensional ordered lyotropic liquid crystals including sponge, cubic, lamella, and hexagonal phases. Natural sugar-based surfactants exhibit the above-mentioned behavior and in addition they posses several advantages over the synthetic ones including high biodegradability, eco-friendly, molecular recognition and less-toxicity. They can self-assemble into specific lyotropic liquid crystalline phases which are stabilized by hydrogen bonds between the sugar moieties. Chirality of the sugar also affects their lyotropic and thermotropic phase behaviors [20, 39]. MEL exhibits the above-mentioned lyotropic liquid crystalline phases. The four classes of MEL with variation in their hydrophilicity show different self-assembling properties including liposomes, self-assembled monolayer, lamella phase, sponge phase, liquid lyotropic crystals and bicontinuous cubic phase [17–21, 39, 43, 70]. Formation of thermodynamically stable vesicle by MEL Mannosylerythritol lipids form thermodynamically stable vesicle (Lα1) from the sponge phase (L3), when they are mixed with l-α-dilauroylphosphatidyl choline(DLPC) [18]. Since they are negatively curved lipids, mixing DLPC (phospholipids) with this sponge phase, induces the fusion of both the lipids and favors their distribution in the inner monolayer of the vesicle. This causes the asymmetric distribution of the two lipids leading to the formation of thermodynamically stable vesicle (Fig. 7). Smallest sized vesicles (633.3 nm) are obtained at a DLPC mole fraction of 0.3 and it is stable at 25 °C for more than 3 months. Such vesicles formed from the natural glycolipids are most preferable for drug delivery and gene transfer due to their biocompatibility when compared to their synthetic counterparts [18]. Fig. 7 Open in new tabDownload slide Mechanism of formation of thermodynamically stable vesicles by MEL-A/DLPC mixture [16]. L 3 MEL sponge phase; L α1 thermodynamically stable vesicle; L α Large multilamellar vesicle (○ - MEL-A negatively curved lipid; ● - DLPC zero curved lipid) Multilamellar vesicles and large unilamellar vesicles Imura et al. [19] studied the self-assembling properties of MEL-A and -B by using fluorescence-probe spectroscopy, dynamic light scattering (DLS) spectroscopy, freeze–fracture transmission electron microscopy (FF-TEM) and synchrotron small/wide-angle X-ray scattering (SAXS/WAXS) spectroscopy. They observed that the MELs self-assemble into large unilamellar vesicles (LUV) just above their critical-aggregation concentration (CAC), which was found to be 4.0 × 10−6 M and 6.0 × 10−6 M for MEL-A and MEL-B, respectively. Above a CAC (II) value of 2.0 × 10−5 M, MEL-A is found to drastically change into sponge like structure (L3) which is composed of a network of randomly connected bilayers with a water-channel diameter of 100 nm and resembles a multicomponent synthetic surfactant system. This channel dimension is relatively large when compared to those obtained with synthetic surfactants. MEL-B, which has a hydroxyl group at the C-4′ position instead of an acetyl group on mannose gives only one CAC. The self-assembled structure of MEL-B seems to gradually move from LUV to multilamellar vesicles (MLV) with lattice constant of 4.4 nm [19]. Lyotropic-liquid-crystalline phases of MEL At high concentrations, the formation of an inverted hexagonal phase (H2) for MEL-A and a lamella phase (Lα) for MEL-B was clearly observed by using polarized optical microscopy. These results indicate that the difference in the spontaneous curvature between MEL-A and MEL-B molecules is due to an extra acetyl group present in MEL-A. This difference decides the direction of their self-assembly. The microorganisms are able to engineer distinct self-assembled structures by varying the substitutions on the polar head group [19]. Imura et al. showed on the phase diagram that MEL-A is able to self-assemble into a variety of distinctive lyotropic liquid crystals including L3, bicontinuous cubic (V2), and lamellar (Lα) phases. The lattice constants are estimated to be 11.39 and 3.58 nm for V2 and Lα, respectively. Differential scanning calorimetry (DSC) measurement revealed that the phase transition enthalpies from these Lyotropic liquid crystals (LCs) to the fluid isotropic (FI) phase are in the range of 0.22–0.44 kJ/mol. L3 region of MEL-A is spread considerably over a wide temperature range (20–65 °C) when compared to that of other surfactants [20]. This is probably due to its unique structure which is molecularly engineered by the microorganisms. MEL-B from P. tsukubaensis (yield 20 g/L) has 1-O-β-(2′,3′-di-O-alka(e)noyl-6′-O-acetyl-d-mannopyranosyl)-d-erythritol (Fig. 6) [12], which is a diastereomer of the conventional MEL-B. This new diastereomer self-assembles into a lamellar (Lα) phase over a remarkably wide range of concentrations and temperatures whereas MEL-A (diacetyl) forms L3, V2, and Lα phases. It is observed that the difference in the number of acetyl groups and the configuration of erythritol moiety play an important role in the aqueous-phase behavior of MEL/water mixture. The interplanar distance (d) of Lα phase of MEL-B is estimated to be 4.7 nm at low concentrations (≤60 wt%) and this d-spacing decreases with increase in concentration (~3.1 nm at >60%). This phase is found to be stable up to 95 °C and below a concentration of 85% (wt). The melting temperature of the liquid crystalline phase dramatically decreases with increase in MEL-B concentration (above 85 wt%). The MEL-B is able to form vesicle of dimension 1–5 μm [70]. MEL-C from P. Siamensis CBS 9960 forms liquid crystal phases such as hexagonal (H) and Lα phases at a wide range of concentrations [51]. Coacervate formation of natural glycolipids Coacervate is a spherical aggregation of lipid molecules making up a colloidal inclusion, which is held together by hydrophobic forces. Coacervate formation by MEL-A and vesicle formation by MEL-B have been observed and as mentioned before this difference arises due to the presence of 4′-O-acetyl group in MEL-B [17]. Self-assembled monolayer structures of MEL MEL-A has been used as a model to understand the role of molecular interaction between glycolipids and proteins in biological recognition events including cell adhesion, signal transduction and immune function. MEL exhibits highly ordered self-assemblies and affinity towards glycoproteins. Self-assembled monolayers (SAMs) of MEL on the alkanethiol SAMs using MEL-A bilayer membrane structures are called supported “Hybrid Bilayer Membranes” (HBMs) (Fig. 8). The interaction between the HBMs and two different immunoglobulins namely HIgG and HIgM was studied by using surface plasmon resonance (SPR) and atomic force microscopy (AFM). The affinity constants (K a) between SAM and HIgG and HIgM are 9.4 × 106 M−1 and 5.4 × 106 M−1, respectively. The binding affinity between the self-assembled monolayer of MEL-A and HIgG is 25 times higher than that observed with Staphylococus aureus protein A which is very commonly used for the purification of HIgG. Also it is six times higher than that observed with MEL-A and poly (2-hydroxyethyl methacrylate) (PHEMA) [21]. MEL-A SAMs on alkanethiolates are well aligned along the surface when compared to those on polymer surfaces prepared by the solvent evaporation method. Although the individual carbohydrate and protein interaction is relatively weak (K a ~ 103 to 104 M−1), the high binding affinity observed here can be attributed to the multivalent effect of the self-assembled monolayer of MEL [19, 21, 43]. Table 4 summarizes the different classes of MELs and their corresponding self-assembling properties. Fig. 8 Open in new tabDownload slide Schematic representation of a hybrid bilayer membrane and molecular interaction [19] Homologs of MEL and their self-assembling properties Type of MEL . Size of the vesicles (μm) . Critical aggregation concentration (M) . Self-assembling structures . Referenes . MEL-A 1–20 4.0 × 10−6 Spherical droplet, Large unilamellar vesicles (LUV) sponge (L3), bicontinuous cubic (V2) and lamella [17–20, 39] Conventional MEL-B 1–20 6.0 × 10−6 Giant vesicles, multi lamellar vesicles (MLV) [17, 19, 39] MEL-B (new diastereomer P. tsukubaensis) 1–5 NA Lamellar (Lα) phase over a wide concentration and temperature ranges, vesicle [67] MEL-C NA NA Myelines and lamella (Lα) [46] MEL-C from P. siamensis CBS 9960 NA NA Hexagonal (H) and lamella (Lα) [57] Type of MEL . Size of the vesicles (μm) . Critical aggregation concentration (M) . Self-assembling structures . Referenes . MEL-A 1–20 4.0 × 10−6 Spherical droplet, Large unilamellar vesicles (LUV) sponge (L3), bicontinuous cubic (V2) and lamella [17–20, 39] Conventional MEL-B 1–20 6.0 × 10−6 Giant vesicles, multi lamellar vesicles (MLV) [17, 19, 39] MEL-B (new diastereomer P. tsukubaensis) 1–5 NA Lamellar (Lα) phase over a wide concentration and temperature ranges, vesicle [67] MEL-C NA NA Myelines and lamella (Lα) [46] MEL-C from P. siamensis CBS 9960 NA NA Hexagonal (H) and lamella (Lα) [57] NA not available Open in new tab Homologs of MEL and their self-assembling properties Type of MEL . Size of the vesicles (μm) . Critical aggregation concentration (M) . Self-assembling structures . Referenes . MEL-A 1–20 4.0 × 10−6 Spherical droplet, Large unilamellar vesicles (LUV) sponge (L3), bicontinuous cubic (V2) and lamella [17–20, 39] Conventional MEL-B 1–20 6.0 × 10−6 Giant vesicles, multi lamellar vesicles (MLV) [17, 19, 39] MEL-B (new diastereomer P. tsukubaensis) 1–5 NA Lamellar (Lα) phase over a wide concentration and temperature ranges, vesicle [67] MEL-C NA NA Myelines and lamella (Lα) [46] MEL-C from P. siamensis CBS 9960 NA NA Hexagonal (H) and lamella (Lα) [57] Type of MEL . Size of the vesicles (μm) . Critical aggregation concentration (M) . Self-assembling structures . Referenes . MEL-A 1–20 4.0 × 10−6 Spherical droplet, Large unilamellar vesicles (LUV) sponge (L3), bicontinuous cubic (V2) and lamella [17–20, 39] Conventional MEL-B 1–20 6.0 × 10−6 Giant vesicles, multi lamellar vesicles (MLV) [17, 19, 39] MEL-B (new diastereomer P. tsukubaensis) 1–5 NA Lamellar (Lα) phase over a wide concentration and temperature ranges, vesicle [67] MEL-C NA NA Myelines and lamella (Lα) [46] MEL-C from P. siamensis CBS 9960 NA NA Hexagonal (H) and lamella (Lα) [57] NA not available Open in new tab Applications MELs are considered as molecules of multifunctionality due to their exceptional surface activity; high yield (above 100 g/L); biocompatibility; self-assembling properties; antimicrobial activities; and biochemical functions [13, 59]. Antimicrobial activity of MEL Both MEL-A and MEL-B show strong activity against gram positive bacteria, weak activity against gram negative bacteria and no activity against fungi. The minimum inhibitory concentrations against gram-positive bacteria are significantly lower than those of sucrose and sorbitan monoesters of fatty acids. Other MELs accumulated in the cell of Schizonella melanogramma also exhibit antibacterial and antifungal activities [5]. Matsumura et al. reported that mannopyranosyl groups are the most effective amongst the n-alkyl glycosides tested against microorganisms. It may not be difficult to enhance the antimicrobial activity of the present MELs further by the chemical modification of the sugar moiety [37]. MEL induces cell differentiation and apoptosis MEL-A and -B have excellent growth inhibition and differentiation-inducing activities against human leukemia cells including myelogenous leukemia cell K562 [26], promyelocytic leukemia cell HL60 [25, 26] and the human basophilic leukemia cell line KU812 [25, 42]. Both inhibit the growth of HL60 cells at concentrations between 5 and 10 μM and also induce changes to their morphology. They (at 10 mg/L) also induce granulocytic differentiation [27, 42] and inhibit the activity of phospholipid- and Ca2+-dependent protein kinase C in HL 60 cells. MEL-A inhibits the serine/threonine phosphorylation of a 30 kDa protein in HL-60 cells and the tyrosine phosphorylation of 55-, 65-, 95-, 135-kDa proteins in K562 cells [42]. Therefore, MEL appears to directly affect intracellular signal transduction through phosphate cascade systems. Both induce significantly the neurite outgrowth of rat pheochromocytoma PC-12 cells and partial cellular differentiation [42, 68]. MEL-A has been recently demonstrated to inhibit the growth of mouse melanoma B 16 cells in a dose-dependent manner. At 10 μM concentration it causes the condensation of chromatin, fragmentation of DNA, and arrest of sub-G1, which indicates that the cells are undergoing apoptosis. MEL is also found to induce tyrosinase activity and enhances the production of melanin [71]. This trigger of mouse melanoma B 16 cells may be through a signaling pathway that involves protein kinase Cα (PKCα) [73]. Purification of glycoprotein MEL-A, -B and -C exhibit high binding affinity to human immunoglobulins [15, 16, 39, 43]. They also show binding affinity towards Ig M and other glycoproteins. Self-assembled monolayer of MEL-A show six times higher affinity than the immobilized MEL-A in PHEMA [21]. All these results show their potential application as a ligand for the purification of lectins. Vehicles for gene delivery MELs can be used as a vehicle for gene and drug delivery due to their ability to form thermodynamically stable vesicles with the ability to fuse with the membrane [23, 24, 43, 65, 66]. Among various biosurfactants, MEL-A provides the highest sufficiency [24]. It remarkably accelerates the adhesion of positively charged liposome–DNA complex to the cell membrane and incorporates this complex into the cell [23, 43]. Inhibit ice agglomeration Ice slurry systems are finding wide applications as environmental friendly cold thermal storage units, especially as air conditioners [22, 42]. In these units, there is a possibility for the ice particles to agglomerate or grow together and block the pipeline, causing superfluous power loads thereby leading to loss of efficiency. MEL at low concentration (10 mg/L) gets adsorbed on the ice surface and suppresses the agglomeration of ice particles. Their effective performance has also been tested successfully in a large scale model (300 L) [22, 41, 42]. Future perspectives The past 60 years of research on MEL has proved that it is the most promising microbial extracellular glycolipid ever known because of its high yield, excellent surface activity, diverse biochemical functions, biocompatibility and its wide range of applications. However, the commercial viability of MEL depends upon its production cost which has to be significantly lowered with the help of recent developments in bioprocess technology together with the advanced separation techniques. Hence the following research topics need to be explored: Reduce the production cost by using cheaper raw material, optimize the production conditions together with downstream processes. Engineer the overproducing mutant and recombinant strains. Develop structure-activity relationship to tailor the compounds with the required features. This can be done by making derivatives (by chemical or enzymatic synthesis and modifications) and analyzing their corresponding performance. Study on the various factors that determine the self-assembling properties to enhance their scope of applications in the biomedical field. Identify the enzymes involved in their biosynthesis and regulate or augment the production of only one type of MEL with higher yield. Determine the role of cell wall components (of Candida sp. Torulopsis sp. and Pseudozyma sp.) and understand how they tolerate high levels of MEL. This may provide new approaches to increase the yield as well as this knowledge could be extrapolated for other classes of BSs. Since MEL can interact with glycoproteins (lectins), use them as model systems to study the mechanism of different biochemical functions. Application of MEL as a vehicle for drug and gene delivery. Establish mechanisms of antimicrobial and antitumor activities of MEL. Similarity studies on the enzymes involved in the synthesis of different classes of glycolipid (rhamnolipids, sophorolipids, cellobiose lipids, MEL, etc.) may give insight into the active site specificity of enzymes for the synthesis of particular kind of glycolipid. Understand the role of MEL production in microbial physiology. Conclusion Mannosylerythritol lipid, 2,3-di-O-alka(e)noyl-β- d-mannopyranosyl-(1 → 4)-O-meso-erythritol, partially acetylated at C4 and/or C6 position, is produced by Ustilago sp., Schizonella sp., and Pseudozyma sp. The type of MEL produced varies with the strains and the species of Pseudozyma. Hence its production can be used as an important taxonomic index to identify Pseudozyma yeast. This is considered as a most promising biosurfactant because of its high yield, excellent surface activity, diverse biochemical functions and biocompatibility. MELs exhibit interesting self-assembling properties which enhance their efficiency in gene transfection. Recent research on the ability of MEL-A to form water-in-oil microemulsion without the use of a cosurfactant seems to add an impetus to the development of the microemulsion technology which is limited due to the fact that they require cosurfactants, salts or alcohols for stabilization. MEL induces differentiation of several carcinoma cell lines. They exhibit antimicrobial and antitumor activities. The high binding affinity of the monolayer of MEL-A to the immunoglobulins helps in the purification of lectins. However their large scale production and recovery processes have to be optimized in order to compete economically with the chemical surfactants. Even though enormous information is available on the growing number of microorganisms that produce MEL with unique physico-chemical properties, very less knowledge is available on the enzymes involved in each step of its synthesis. Its regulation, structure–function relationship, mechanism of its biochemical functions like differentiation on carcinoma cell lines are poorly understood and needs major research thrust. References 1. Bhattacharjee SS , Haskins RH, Gorin PAJ Location of acyl groups on two partly acylated glycolipids from strains of Ustilago (smut fungi) Carbohydr Res 1970 13 235 246 10.1016/S0008-6215(00)80830-7 Google Scholar Crossref Search ADS WorldCat 2. Boothroyd B , Thorn JA, Haskins RH Biochemistry of the ustilaginales. XII. Characterization of extracellular glycolipids produced by Ustilago sp Can J Biochem Physiol 1956 34 10 14 Google Scholar Crossref Search ADS PubMed WorldCat 3. Cameotra SS , Makkar RS Recent applications of biosurfactants as biological and immunological molecules Curr Opin Microbiol 2004 7 262 266 10.1016/j.mib.2004.04.006 Google Scholar Crossref Search ADS PubMed WorldCat 4. Davey ME , Caiazza NC, OToole GA Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1 J Bacteriol 2003 185 1027 1036 10.1128/JB.185.3.1027-1036.2003 Google Scholar Crossref Search ADS PubMed WorldCat 5. Deml G , Anke T, Oberwinkler F, Gianetti BM, Steglich W Schizonellin A and B, new glycolipids from Schizonella melanogramma Phytochemistry 1980 19 83 87 10.1016/0031-9422(80)85018-7 Google Scholar Crossref Search ADS WorldCat 6. Desai JD , Banat IM Microbial production of surfactants and their commercial potential Microbiol Mol Biol Rev 1997 61 47 64 Google Scholar Crossref Search ADS PubMed WorldCat 7. Deziel E , Lepine F, Milot S, Villemur R rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroyalkanoyloxy)alkanoic acids (HAAs), the precursors of rhamnolipids Microbiology 2003 149 2005 2013 10.1099/mic.0.26154-0 Google Scholar Crossref Search ADS PubMed WorldCat 8. Fluharty AL , O’Brien JS A mannose- and erythritol-containing glycolipid from Ustilago maydis Biochemistry 1969 8 2627 2632 10.1021/bi00834a056 Google Scholar Crossref Search ADS PubMed WorldCat 9. Fukuoka T , Morita T, Konishi M, Imura T, Kitamoto D Characterization of new glycolipid biosurfactants, tri-acylated mannosylerythritol lipids, produced by Pseudozyma yeasts Biotechnol Lett 2007 29 1111 1118 10.1007/s10529-007-9363-0 Google Scholar Crossref Search ADS PubMed WorldCat 10. Fukuoka T , Morita T, Konishi M, Imura T, Kitamoto D Characterisation of new types of mannosylerythritol lipids as biosurfactants produced from soybean oil by a Basidiomycetes yeast, Pseudozyma shanxiensis J Oleo Sci 2007 56 435 442 Google Scholar Crossref Search ADS PubMed WorldCat 11. Fukuoka T , Morita T, Konishi M, Imura T, Sakai H, Kitamoto D Structural characterization and surface-active properties of a new glycolipid biosurfactant, mono-acylated mannosylerythritol lipid, produced from glucose by Pseudozyma antarctica Appl Microbiol Biotechnol 2007 76 801 810 10.1007/s00253-007-1051-4 Google Scholar Crossref Search ADS PubMed WorldCat 12. Fukuoka T , Morita T, Konishi M, Imura T, Kitamoto D A basidiomycetous yeast, Pseudozyma tsukubaensis, efficiently produces a novel glycolipid biosurfactant. The identification of a new diastereomer of mannosylerythritol lipid-B Carbohydr Res 2008 343 555 560 10.1016/j.carres.2007.11.023 Google Scholar Crossref Search ADS PubMed WorldCat 13. Hamme JDV , Singh A, Ward OP Physiological aspects Part 1 in a series of papers devoted to surfactants in microbiology and biotechnology Biotechnol Adv 2006 24 604 620 10.1016/j.biotechadv.2006.08.001 Google Scholar Crossref Search ADS PubMed WorldCat 14. Haskins RH , Thorn JA, Boothroyd B Biochemistry of the ustilagenales. XI. Metabolic products of Ustilago zeae in submerged culture Can J Microbiol 1955 1 749 756 10.1139/m55-089 Google Scholar Crossref Search ADS PubMed WorldCat 15. Im JH, Nakane T, Yanagishita H, Ikegami T, Kitamoto D (2001) Mannosylerythritol lipid, a yeast extracellular glycolipid, shows high binding affinity towards human immunoglobulin G. BMC Biotechnol 1:5. http://www.biomedcentral.com/1472-6750/1/5. doi:10.1186/1472-6750-1-5 16. Im JH , Yanagishita H, Ikegami T, Takeyama Y, Idemoto Y, Koura Net al. Mannosylerythritol lipids, yeast glycolipid biosurfactants, are potential affinity ligand materials for human immunoglobulin G J Biomed Mater Res 2003 65A 379 385 10.1002/jbm.a.10491 Google Scholar Crossref Search ADS WorldCat 17. Imura T , Yanagishita H, Kitamoto D Coacervate formation from natural glycolipid: one acetyl group on the headgroup triggers coacervate-to-vesicle transition J Am Chem Soc 2004 126 10804 10805 10.1021/ja0400281 Google Scholar Crossref Search ADS PubMed WorldCat 18. Imura T , Yanagishita H, Ohira J, Sakai H, Abeb M, Kitamoto D Thermodynamically stable vesicle formation from glycolipid biosurfactant sponge phase Colloids Surf B Biointerfaces 2005 43 115 121 10.1016/j.colsurfb.2005.03.015 Google Scholar Crossref Search ADS PubMed WorldCat 19. Imura T , Ohta N, Inoue K, Yagi N, Negishi H, Yanagishita Het al. Naturally engineered glycolipid biosurfactants leading to distinctive self-assembled structures Chem Eur J 2006 12 2434 2440 10.1002/chem.200501199 Google Scholar Crossref Search ADS PubMed WorldCat 20. Imura T , Hikosaka Y, Worakitkanchanakul W, Sakai H, Abe M, Konishi Met al. Aqueous-phase behavior of natural glycolipid biosurfactant mannosylerythritol lipid A: sponge, cubic, and lamellar phases Langmuir 2007 23 1659 1663 10.1021/la0620814 Google Scholar Crossref Search ADS PubMed WorldCat 21. Imura T , Ito S, Azumi R, Yanagishita H, Sakai H, Abe Met al. Monolayers assembled from a glycolipid biosurfactant from Pseudozyma (Candida) antarctica serve as a high-affinity ligand system for immunoglobulin G and M Biotechnol Lett 2007 29 865 870 10.1007/s10529-007-9335-4 Google Scholar Crossref Search ADS PubMed WorldCat 22. Inaba H New challenge in advanced thermal energy transportation using functionally thermal fluids Int J Therm Sci 2000 39 991 1003 10.1016/S1290-0729(00)01191-1 Google Scholar Crossref Search ADS WorldCat 23. Inoh Y , Kitamoto D, Hirashima N, Nakanishi M Biosurfactants of MEL-A increase gene transfection mediated by cationic liposomes Biochem Biophys Res Commun 2001 289 57 61 10.1006/bbrc.2001.5930 Google Scholar Crossref Search ADS PubMed WorldCat 24. Inoh Y , Kitamoto D, Hirashima N, Nakanishi M Biosurfactant MEL-A dramatically increases gene transfection via membrane fusion J Control Release 2004 94 423 431 10.1016/j.jconrel.2003.10.020 Google Scholar Crossref Search ADS PubMed WorldCat 25. Isoda H , Kitamoto D, Shinmoto H, Matsumura M, Nakahara T Microbial extracellular glycolipid induction of differentiation and inhibition of the protein kinase C activity of human promyelocytic leukemia cell line HL60 Biosci Biotechnol Biochem 1997 61 609 614 Google Scholar Crossref Search ADS PubMed WorldCat 26. Isoda H , Shinmoto H, Kitamoto D, Matsumura M, Nakahara T Differentiation of human promyelocytic leukemia cell line HL60 by microbial extracellular glycolipids Lipids 1997 32 263 271 10.1007/s11745-997-0033-0 Google Scholar Crossref Search ADS PubMed WorldCat 27. Isoda H , Nakahara T Mannosylerythritol lipid induces granulocytic differentiation and inhibits the tyrosine phosphorylation of human myelogenous leukemia cell line K562 Cytotechnology 1997 25 191 195 10.1023/A:1007982909932 Google Scholar Crossref Search ADS PubMed WorldCat 28. Kakugawa K , Tamai M, Imamura K, Miyamoto K, Miyoshi S, Morinaga Yet al. Isolation of yeast Kurtzmanomyces sp. I-11, novel producer of mannosylerythritol lipid Biosci Biotechnol Biochem 2002 66 188 191 10.1271/bbb.66.188 Google Scholar Crossref Search ADS PubMed WorldCat 29. Kawashima H , Nakahara T, Oogaki M, Tabuchi T Extracellular production of a mannosylerythritol lipid by a mutant of Candida sp. from n-alkanes and triacylglycerols J Ferment Technol 1983 61 143 149 Google Scholar OpenURL Placeholder Text WorldCat 30. Kearns DB , Losick R Swarming motility in undomesticated Bacillus subtilis Mol Microbiol 2003 49 581 590 10.1046/j.1365-2958.2003.03584.x Google Scholar Crossref Search ADS PubMed WorldCat 31. Kim H-S , Yoon BD, Choung DH, Oh HM, Katsuragi T, Tani Y Characterization of a biosurfactant, mannosylerythritol lipid produced from Candida sp SY16 Appl Microbiol Biotechnol 1999 52 713 721 10.1007/s002530051583 Google Scholar Crossref Search ADS PubMed WorldCat 32. Kim H-S , Jeon J-W, Kim B-H, Ahn C-Y, Oh H-M, Yoon B-D Extracellular production of a glycolipid biosurfactant, mannosylerythritol lipid, by Candida sp. SY16 using fed-batch fermentation Appl Microbiol Biotechnol 2006 70 391 396 10.1007/s00253-005-0092-9 Google Scholar Crossref Search ADS PubMed WorldCat 33. Kitamoto D , Akiba S, Hioki C, Tabuchi T Extracellular accumulation of mannosylerythritol lipids by a strain of Candida antarctica Agric Biol Chem 1990 54 31 36 Google Scholar OpenURL Placeholder Text WorldCat 34. Kitamoto D , Haneishi K, Nakahara T, Tabuchi T Production of mannosylerythritol lipids by Candida antarctica from vegetable oils Agric Biol Chem 1990 54 37 40 Google Scholar OpenURL Placeholder Text WorldCat 35. Kitamoto D , Fuzishiro T, Yanagishita H, Nakane T, Nakahara T Production of mannosylerythritol lipids as biosurfactants by resting cells of Candida antarctica Biotechnol Lett 1992 14 305 310 10.1007/BF01022329 Google Scholar Crossref Search ADS WorldCat 36. Kitamoto D , Nemoto T, Yanagishita H, Nakane T, Kitamoto H, Nakahara T Fatty acid metabolism of mannosylerythritol lipids as biosurfactants produced by Candida antarctica J Jpn Oil Chem Soc 1993 42 346 358 Google Scholar Crossref Search ADS WorldCat 37. Kitamoto D , Yanagishita H, Shinbo T, Nakane T, Kamisawa C, Nakahara T Surface active properties and antimicrobial activities of mannosylerythritol lipids as biosurfactants produced by Candida antarctica J Biotechnol 1993 29 91 96 10.1016/0168-1656(93)90042-L Google Scholar Crossref Search ADS WorldCat 38. Kitamoto D , Yanagishita H, Hayara K, Kltamoto HK Contribution of a chain-shortening pathway to the biosynthesis of the fatty acids of mannosyierythritol lipid (biosurfactant) in the yeast Candida antarctica: effect of β-oxidation inhibitors on biosurfactant synthesis Biotechnol Lett 1998 20 813 818 10.1023/A:1005347022247 Google Scholar Crossref Search ADS WorldCat 39. Kitamoto D , Ghosh SGO, Nakatani Y Formation of giant vesicle from diacylmannosylerythritols and their binding to concanavalin A Chem Commun 2000 2000 861 862 10.1039/b000968g Google Scholar Crossref Search ADS WorldCat 40. Kitamoto D , Ikegami T, Suzuki GT, Sasaki A, Takeyama Y, Idemoto Yet al. Microbial conversion of n-alkanes into glycolipid biosurfactants, mannosylerythritol lipids, by Pseudozyma (Candida antarctica) Biotechnol Lett 2001 23 1709 1714 10.1023/A:1012464717259 Google Scholar Crossref Search ADS WorldCat 41. Kitamoto D , Yanagishita H, Endo A, Nakaiwa M, Nakane M, Akiya T Remarkable antiagglomeration effect of a yeast biosurfactant, diacylmannosylerythritol, on ice-water slurry for cold thermal storage Biotechnol Prog 2001 17 362 365 10.1021/bp000159f Google Scholar Crossref Search ADS PubMed WorldCat 42. Kitamoto D , Isoda H, Nakahara T Functions and potential applications of glycolipid biosurfactants-from energy-saving materials to gene delivery carriers J Biosci Bioeng 2002 94 187 201 10.1263/jbb.94.187 Google Scholar Crossref Search ADS PubMed WorldCat 43. Kitamoto D Naturally engineered glycolipid biosurfactants leading to distinctive self-assembling properties Yakugaku Zasshi 2008 128 695 706 10.1248/yakushi.128.695 Google Scholar Crossref Search ADS PubMed WorldCat 44. Konishi M , Imura T, Fukuoka T, Morita T, Kitamoto D A yeast glycolipid biosurfactant, mannosylerythritol lipid, shows high binding affinity towards lectins on a self-assembled monolayer system Biotechnol Lett 2007 29 473 480 10.1007/s10529-006-9261-x Google Scholar Crossref Search ADS PubMed WorldCat 45. Konishi M , Morita T, Fukuoka T, Imura T, Kakugawa K, Kitamoto D Production of different types of mannosylerythritol lipids as biosurfactants by the newly isolated yeast strains belonging to the genus Pseudozyma Appl Microbiol Biotechnol 2007 75 521 531 10.1007/s00253-007-0853-8 Google Scholar Crossref Search ADS PubMed WorldCat 46. Konishi M , Morita T, Fukuoka T, Imura T, Kakugawa K, Kitamoto D Efficient production of mannosylerythritol lipids with high hydrophilicity by Pseudozyma hubeiensis KM-59 Appl Microbiol Biotechnol 2008 78 37 46 10.1007/s00253-007-1292-2 Google Scholar Crossref Search ADS PubMed WorldCat 47. Matsuyama T , Nakagawa Y Bacterial wetting agents working incolonization of bacteria on surface environments Colloids Surf B Biointerfaces 1996 7 207 214 10.1016/0927-7765(96)01300-8 Google Scholar Crossref Search ADS WorldCat 48. Morita T , Konishi M, Fukuoka T, Imura T, Kitamoto D Discovery of Pseudozyma rugulosa NBRC 10877 as a novel producer of the glycolipid biosurfactants, mannosylerythritol lipids, based on rDNA sequence Appl Microbiol Biotechnol 2006 73 305 313 10.1007/s00253-006-0466-7 Google Scholar Crossref Search ADS PubMed WorldCat 49. Morita T , Konishi M, Fukuoka T, Imura T, Kitamoto HK, Kitamoto D Characterization of the genus Pseudozyma by the formation of glycolipid biosurfactants, mannosylerythritol lipids FEMS Yeast Res 2007 7 286 292 10.1111/j.1567-1364.2006.00154.x Google Scholar Crossref Search ADS PubMed WorldCat 50. Morita T , Konishi M, Fukuoka T, Imura T, Yamamoto S, Kitagawa Met al. Identification of Pseudozyma graminicola CBS 10092 as a producer of glycolipid biosurfactants, mannosylerythritol lipids J Oleo Sci 2008 57 123 131 Google Scholar Crossref Search ADS PubMed WorldCat 51. Morita T , Konishi M, Fukuoka T, Imura T, Kitamoto D Production of glycolipid biosurfactants, mannosylerythritol lipids, by Pseudozyma siamensis CBS 9960 and their interfacial properties J Biosci Bioeng 2008 105 493 502 10.1263/jbb.105.493 Google Scholar Crossref Search ADS PubMed WorldCat 52. Mulligan CN Environmental applications for biosurfactants Environ Pollut 2005 133 183 198 10.1016/j.envpol.2004.06.009 Google Scholar Crossref Search ADS PubMed WorldCat 53. Neu TR Significance of bacterial surface-active compounds in interaction of bacteria with interfaces Microbiol Rev 1996 60 151 166 Google Scholar Crossref Search ADS PubMed WorldCat 54. Rau U , Nguyen LA, Schulz S, Wray V, Nimtz M, Roeper Het al. Formation and analysis of mannosylerythritol lipids secreted by Pseudozyma aphidis Appl Microbiol Biotechnol 2005 66 551 5593 10.1007/s00253-004-1672-9 Google Scholar Crossref Search ADS PubMed WorldCat 55. Rau U , Nguyen LA, Roeper H, Koch H, Lang S Fed-batch bioreactor production of mannosylerythritol lipids secreted by Pseudozyma aphidis Appl Microbiol Biotechnol 2005 68 607 613 10.1007/s00253-005-1906-5 Google Scholar Crossref Search ADS PubMed WorldCat 56. Rau U , Nguyen LA, Roeper H, Koch H, Lang S Downstream processing of mannosylerythritol lipids produced by Pseudozyma aphidis Eur J Lipid Sci Technol 2005 107 373 380 10.1002/ejlt.200401122 Google Scholar Crossref Search ADS WorldCat 57. Rodrigues L , Banat IM, Teixeira J, Oliveira R Biosurfactants: potential applications in medicine J Antimicrob Chemother 2006 57 609 618 10.1093/jac/dkl024 Google Scholar Crossref Search ADS PubMed WorldCat 58. Ron EZ , Rosenberg E Natural roles of biosurfactants Environ Microbiol 2001 3 229 236 10.1046/j.1462-2920.2001.00190.x Google Scholar Crossref Search ADS PubMed WorldCat 59. Rosenberg E , Ron EZ High- and low-molecular-mass microbial surfactants Appl Microbiol Biotechnol 1999 52 154 162 10.1007/s002530051502 Google Scholar Crossref Search ADS PubMed WorldCat 60. Shibahara M , Zhao X, Wakamatsu Y, Nomura N, Nakahara T, Jin Cet al. Mannosylerythritol lipid increases levels of galactoceramide in and neurite outgrowth from PC12 pheochromocytoma cells Cytotechnology 2000 33 247 251 10.1023/A:1008155111024 Google Scholar Crossref Search ADS PubMed WorldCat 61. Singh A , Van Hamme JD, Ward OP Surfactants in microbiology and biotechnology. Part 2. Application aspects Biotechnol Adv 2007 25 99 121 10.1016/j.biotechadv.2006.10.004 Google Scholar Crossref Search ADS PubMed WorldCat 62. Singh P , Cameotra SS Potential applications of microbial surfactants in biomedical sciences Trends Biotechnol 2004 22 142 146 10.1016/j.tibtech.2004.01.010 Google Scholar Crossref Search ADS PubMed WorldCat 63. Spoeckner S , Wray V, Nimtz M, Lang S Glycolipids of the smut fungus Ustilago maydis from cultivation on renewable resources Appl Microbiol Biotechnol 1999 51 33 39 10.1007/s002530051359 Google Scholar Crossref Search ADS WorldCat 64. Tanaka A, Fukui S (1989) Metabolism of n-alkane. In: The yeast, vol 3, 2nd edn. Academic Press, London, p 261–287 65. Ueno Y , Hirashima N, Inoh Y, Furuno T, Nakanishi M Characterization of biosurfactant-containing liposomes and their efficiency for gene transfection Biol Pharm Bull 2007 30 169 172 10.1248/bpb.30.169 Google Scholar Crossref Search ADS PubMed WorldCat 66. Ueno Y , Inoh Y, Furuno T, Hirashima N, Kitamoto D, Nakanishi M NBD-conjugated biosurfactant (MEL-A) shows a new pathway for transfection J Control Release 2007 123 247 253 10.1016/j.jconrel.2007.08.012 Google Scholar Crossref Search ADS PubMed WorldCat 67. Vertesy L, Kurz M, Wink J, Noelken G (2002) Ustilipides, method for the production and the use thereof. US Patent 6,472,158 68. Wakamatsu Y , Zhao X, Jin C, Day N, Shibahara M, Nomura Net al. Mannosylerythritol lipid induces characteristics of neuronal differentiation in PC12 cells through an ERK-related signal cascade Eur J Biochem 2001 268 374 383 10.1046/j.1432-1033.2001.01887.x Google Scholar Crossref Search ADS PubMed WorldCat 69. Wander RJA , Vreken P, Ferdiandusse S, Jansen GA, Waterham HR, van Roermunde CWTet al. Peroxisomal fatty acid α- and β-oxida tion in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases Biochem Soc Trans 2001 29 250 267 10.1042/BST0290250 Google Scholar Crossref Search ADS PubMed WorldCat 70. Worakitkanchanakula W, Imurab T, Fukuokab T, Moritab T, Sakaia H, Abea M et al. (2008) Aqueous-phase behavior and vesicle formation of natural glycolipid biosurfactant, mannosylerythritol lipid-B. Colloids Surf B Biointerfaces. doi:10.1016/j.colsurfb.2008.03.009 71. Zhao X , Wakamatsu Y, Shibahara M, Nomura N, Geltinger C, Nakahara Tet al. Mannosylerythritol lipid is a potent inducer of apoptosis and differentiation of mouse melanoma cells in culture Cancer Res 1999 59 482 486 Google Scholar PubMed OpenURL Placeholder Text WorldCat 72. Zhao X , Geltinger X, Kishikawa S, Ohshima S, Murata S, Nomura Set al. Treatment of mouse melanoma cells with phorbol 12-myristate 13-acetate counteracts mannosylerythritollipid-induced growth arrest and apoptosis Cytotechnology 2000 33 123 130 10.1023/A:1008129616127 Google Scholar Crossref Search ADS PubMed WorldCat 73. Zhao X , Murata T, Ohno S, Day N, Song J, Nomura Net al. Protein kinase Cα plays a critical role in mannosylerythritol lipid-induced differentiation of melanoma B16 Cells J Biol Chem 2001 276 39903 39910 10.1074/jbc.M010281200 Google Scholar Crossref Search ADS PubMed WorldCat © Society for Industrial Microbiology 2008 This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © Society for Industrial Microbiology 2008
TI - Mannosylerythritol lipids: a review
JF - Journal of Industrial Microbiology and Biotechnology
DO - 10.1007/s10295-008-0460-4
DA - 2008-12-01
UR - https://www.deepdyve.com/lp/oxford-university-press/mannosylerythritol-lipids-a-review-Wa65UW8hWQ
SP - 1559
EP - 1570
VL - 35
IS - 12
DP - DeepDyve
ER -