TY - JOUR
AU1 - Korhola, Matti
AB - Abstract I was fortunate to enter yeast research at the Alko Research Laboratories with a strong tradition in yeast biochemistry and physiology studies. At the same time in the 1980s there was a fundamental or paradigm change in molecular biology research with discoveries in DNA sequencing and other analytical and physical techniques for studying macromolecules and cells. Since that time biotechnological research has expanded the traditional fermentation industries to efficient production of industrial and other enzymes and specialty chemicals. Our efforts were directed towards improving the industrial production organisms: minerals enriched yeasts (Se, Cr, Zn) and high glutathione content yeast, baker´s, distiller´s, sour dough and wine yeasts, and the fungal Trichoderma reesei platform for enzyme production. I am grateful for the trust of my colleagues in several leadership positions at the Alko Research Laboratories, Yeast Industry Platform and at the international yeast community. Alko Research Laboratories, alpha-galactosidase, MEL genes, sour dough yeasts, Trichoderma reesei platform, Yeast Industry Platform FROM A QUIET FOREST TO STINKY SULFUR AND ALCOHOL I was born on April Fool´s Day in 1946 in the middle of the Finnish forests on a 1–2 cow small 4-hectare farm that my parents had bought in 1940 and that my mother was taking care of. After fighting against the Soviet Union in the Second World War, my father went into a technical school where he specialized in steam engines. He was also employed for several years on ocean cargo ships sailing mostly to European ports but also to Africa. I still have not been to Africa myself. Life dramatically changed when I was seven years old and we moved to an industrial town. We lived only 50–100 m from a major Finnish pulp mill where my father got a job in its power plant. The sulfur tower for making sulfite liquor with its impressively stinky fumes was just across the road! Later I came to know that the factory also had an alcohol plant for spent sulfite liquor fermentation with yeast and a distillation unit to concentrate ethanol into spirits. That change from the pristine wooded countryside to the city, and industry across the street, probably was a major turning point in my early development. MY PRACTICAL SIDE WINS Unlike many younger yeast investigators, my entry into yeast research didn’t begin until my formal education and post-doctoral training were completed. My early training in microbiology, genetics and biochemistry began in 1967 at the University of Helsinki. I initially majored in genetics and even completed studies for a M.Sc. degree, but possessing a somewhat more practical nature switched to General Microbiology and graduated in 1972. However, after changing to microbiology I continued to work for 2 years as a teaching assistant in microbial genetics in the Department of Genetics under Prof. Esko Suomalainen. He specialized in butterfly karyotypes and the genetics of parthenogenesis and was an early and important supporter as my research career developed. After graduation, I obtained an ASLA-Fulbright scholarship for graduate studies with Prof. Palmer Rogers at the University of Minnesota where I continued my Master's thesis topic, studies of DNA replication in Escherichia coli. ASLA was a USA loan to Finland after the First World War. Fulbright funds were derived from the sales of post-World War II surplus by the USA. I continued with Dr Rogers for two more years taking graduate courses and completing about 90% of the required research for a doctoral dissertation in Finland. I returned to the University of Helsinki in 1975 as a teaching assistant in General Microbiology and also completed my Ph.D. degree 3 years later. RIGHT CONFERENCE—RIGHT TIME Following a stint as a microbiologist at the Finnish Customs Laboratory, I entered industrial research in 1980, joining Alko Ltd Research Laboratories in Helsinki, Finland, a longstanding leader investigating the biochemistry, physiology and structural biology of Saccharomyces cerevisiae. That year I was also introduced to yeast genetics and molecular biology by attending a 3-week EMBO laboratory course on Yeast Genetics in Basel organized by Albert Hinnen, who had discovered the first yeast transformation method while working in Gerald Fink´s laboratory; Francoise Lacroute, a pyrimidine pathway expert; and Jean Beggs, who constructed a widely used high copy number shuttle vector pJDB207. This experience greatly contributed to my success at Alko where I was charged with introducing molecular approaches, especially the recently developed recombinant DNA (rDNA) technologies, into yeast research, industrial enzyme production strain development and later biomedical alcohol research (Fig. 1). Figure 1. View largeDownload slide Top: Participants of the Alko Symposium ‘Gene Expression in Yeast’ in 1983 in Helsinki, Finland. Bottom: Identification of the participants. Nobel Prize winners—nos. 1, J. W. Szostak, nos. 25, M. Rosbash and nos. 28, R. W. Schekman. (Photo & drawing: Kalervo Koski). Figure 1. View largeDownload slide Top: Participants of the Alko Symposium ‘Gene Expression in Yeast’ in 1983 in Helsinki, Finland. Bottom: Identification of the participants. Nobel Prize winners—nos. 1, J. W. Szostak, nos. 25, M. Rosbash and nos. 28, R. W. Schekman. (Photo & drawing: Kalervo Koski). READY OR NOT—YOU’RE IN CHARGE It was at Alko that I got a flying start in 1980 into the world of industrial research. The view of the directors when I was hired was that, if found capable, I would succeed Dr Erkki Oura, one of the early pioneers in systems biology research. This, in fact, occurred 2 years later. The big boss Prof. (h.c.), Dr Heikki Suomalainen, a 40-year leader in yeast research and industrial production, also retired at the same time (Fig. 2, left). Unfortunately, the boss who had hired me, Dr Kalervo Eriksson, suddenly died in 1987 at the age 49 (Fig. 3, top). As a result of these departures, I inherited the whole ‘orchestra’ of yeast and alcohol research with about 100 people in analytical, biomedical and microbial research. Dr Eriksson, well known for his work on genetic basis of alcoholism, used laboratory rats as experimental objects and by breeding and selection established two genetically distinct lines: AA, the Alko Alcohol strain, who preferred 10% ethanol over water and ANA, the Alko Non-Alcohol strain who preferred water as their drink. Figure 2. View largeDownload slide Left: Prof. Heikki Suomalainen, the Industrial Director and Vice Chairman of the Board of Alko Ltd, and the author, Matti Korhola (right) in 1981 after my presentation ‘The Science of Dr Oura’. Right: Prof. Gennadi I. Naumov and the author at the International Congress on Yeasts in 2004 at Rio de Janeiro, Brazil. Figure 2. View largeDownload slide Left: Prof. Heikki Suomalainen, the Industrial Director and Vice Chairman of the Board of Alko Ltd, and the author, Matti Korhola (right) in 1981 after my presentation ‘The Science of Dr Oura’. Right: Prof. Gennadi I. Naumov and the author at the International Congress on Yeasts in 2004 at Rio de Janeiro, Brazil. Figure 3. View largeDownload slide Top: Dr Tor-Magnus Enari, Director of Biotechnological Research at VTT (The State Technical Research Centre, Finland), and Dr Kalervo Eriksson, Director of Industrial Production and Research, and Member of the Board of Alko Ltd in 1981. Dr Enari, while Chairman of the European Brewery Convention, invited the author to deliver the sister industry´s talk at the 1987 EBC Congress in front of 1500 attendees in Madrid, Spain. Bottom: Mrs Kati Oura and Dr Erkki Oura on the occasion of his 60th birthday in 1981. The book consisted of reprints of scientific publications by Dr Oura. Figure 3. View largeDownload slide Top: Dr Tor-Magnus Enari, Director of Biotechnological Research at VTT (The State Technical Research Centre, Finland), and Dr Kalervo Eriksson, Director of Industrial Production and Research, and Member of the Board of Alko Ltd in 1981. Dr Enari, while Chairman of the European Brewery Convention, invited the author to deliver the sister industry´s talk at the 1987 EBC Congress in front of 1500 attendees in Madrid, Spain. Bottom: Mrs Kati Oura and Dr Erkki Oura on the occasion of his 60th birthday in 1981. The book consisted of reprints of scientific publications by Dr Oura. MAKING PEACE WITH THE OUTSIDERS My first impression on joining the company was that I had entered a museum with very old equipment, methodologies and high reservation towards cooperation and organized projects; the employees simply feared change. However, the company's past achievements, high international reputation and resources of their alcohol monopoly convinced me that this was the right place to be. My leading philosophy was to encourage openness, critical thinking and collaboration with colleagues inside and outside of the company. Gradually, this philosophy prevailed and the laboratory's intellectual environment became excellent. My ability to change the Laboratory's attitudes and direction derived in no small part from the fact that Dr Oura hated administrative duties (Fig. 3, bottom). He was an introvert scientist, and almost immediately passed all budget and personnel matters onto me. I immediately started renewing the Fermentation/Microbiology Department by increasing the investment budget 10-fold and hiring promising, young scientists from domestic and foreign institutions. Over the years, I hired mostly Finns who were or developed into senior researchers: Pirjo Lehtinen from The European Molecular Biology Laboratories (EMBL, Germany), Paula Kristo from Baylor College of Medicine, Sirpa Aho from Harvard University, Tuula Torkkeli from Rockefeller University (all three from the USA) and Pirkko Liljeström (now Suominen) from University of Helsinki, Helena Kopu (now Torkkeli) from University of Oulu, Hilkka Turakainen from University of Turku and Helena Nevalainen from The State Technical Research Centre (VTT), Finland (Fig. 1). We also encouraged visits from foreign researchers and took on master’s and doctoral degree students. In the midst of these exciting changes, however, we continuously faced a big problem. Many in the company, especially the financial group, felt the Research Laboratories were predominantly promoting the personal scientific careers of its research staff, particularly that of Prof. Suomalainen. Scientific publications were a real sore point. One of my principle duties became convincing the ‘outsiders’ that we were working in the company's best interest. We initially argued that publications were a great way of compressing our work into gems, and their publications in peer-reviewed journals were great quality control measures. Later on, I hired two patent experts and assuaged my financial colleagues’ criticism by ensuring that patents were considered before publication. MANY RESEARCH PROJECTS—MANY COMMERCIAL PRODUCTS A major difference between industrial and academic research is the variety of projects one encounters during a career and their time-sensitive nature. Mine were expansive (Table 1). Table 1. Products and processes developed. Product/process  Essential feature  Trade name/pilot/academic  Further developments  Reference  Amylolytic yeast  Hormoconis resinae glucoamylase P gene expressed  Academic      Baker’s yeast  High rate of fermentation in lean/sugar dough; classical breeding  LaFlorida  Acidos Organicos SA, Tlalnepantla, Mexico    Brewer’s yeast  Old-fashioned lager Pof—yeast, craft beer yeast  ABM 1326  Alkomohr Biotech Ltd, Helsinki, Finland    Chromium-enriched yeast  Cr biologically bound  Kromona, Lalmin Cr2000  Lallemand Inc., Montreal, Canada    Distiller’s yeast  Ethanol tolerance improved  ALKO 554  Alko Ltd, Helsinki, Finland  Korhola (2010)  Enzymatic fuel cell  Bacterial PQQ-methanol dehydrogenase product application  Pilot  Enfucell Ltd, Vantaa, Finland  US Pat 7384701  Folate yeasts  Folates (Vitamin B9)  Academic    Korhola et al. (2014)  Glutathione yeast  Especially high GSH content  Pilot phase  Lallemand Inc.    Industrial enzymes  Trichoderma reesei genetically engineered production platform  Biotouch, Econase, Ecopulp, Ecostone, Finase, Flashzyme  ROAL/AB Enzymes/ABF Ingredients Ltd, London, UK  Aho et al. (1991); US Pat 5665585  MEL yeasts  Alfa-Galactosidase, MEL genes  AGAL, Rokkaasi (pilot) MEL yeasts (pilot, academic)  Alkomohr Biotech Ltd  Liljeström-Suominen, Joutsjoki and Korhola (1988); US Pat 5055401  Selenium-enriched yeast  Se biologically bound in place of sulfur. L-Se-Met made 60%–75% of bound Se  Alkosel 500, Alkosel 1000, Selena, Lalmin Se1000, Lalmin Se2000, Alkosel 3000, Alkosel R397 Ruminants  Lallemand Inc.  Korhola, Vainio and Edelmann (1986)  Sour dough yeast  Candida milleri  ABM 4949  Alkomohr Biotech Ltd  Mäntynen et al. (1999)  Wine yeast  Low foaming, breeding of homothallic wine yeast strains  Pilot  Lallemand Inc.    Xylose yeast  Barley xylose isomerase cloned into distiller´s yeast (XI inactive)  Academic    Kristo et al. (1996)  Zinc-enriched yeast  Zn biologically bound  Sinkkona, Lalmin Zn50, Servomyces  Lallemand Inc.    Product/process  Essential feature  Trade name/pilot/academic  Further developments  Reference  Amylolytic yeast  Hormoconis resinae glucoamylase P gene expressed  Academic      Baker’s yeast  High rate of fermentation in lean/sugar dough; classical breeding  LaFlorida  Acidos Organicos SA, Tlalnepantla, Mexico    Brewer’s yeast  Old-fashioned lager Pof—yeast, craft beer yeast  ABM 1326  Alkomohr Biotech Ltd, Helsinki, Finland    Chromium-enriched yeast  Cr biologically bound  Kromona, Lalmin Cr2000  Lallemand Inc., Montreal, Canada    Distiller’s yeast  Ethanol tolerance improved  ALKO 554  Alko Ltd, Helsinki, Finland  Korhola (2010)  Enzymatic fuel cell  Bacterial PQQ-methanol dehydrogenase product application  Pilot  Enfucell Ltd, Vantaa, Finland  US Pat 7384701  Folate yeasts  Folates (Vitamin B9)  Academic    Korhola et al. (2014)  Glutathione yeast  Especially high GSH content  Pilot phase  Lallemand Inc.    Industrial enzymes  Trichoderma reesei genetically engineered production platform  Biotouch, Econase, Ecopulp, Ecostone, Finase, Flashzyme  ROAL/AB Enzymes/ABF Ingredients Ltd, London, UK  Aho et al. (1991); US Pat 5665585  MEL yeasts  Alfa-Galactosidase, MEL genes  AGAL, Rokkaasi (pilot) MEL yeasts (pilot, academic)  Alkomohr Biotech Ltd  Liljeström-Suominen, Joutsjoki and Korhola (1988); US Pat 5055401  Selenium-enriched yeast  Se biologically bound in place of sulfur. L-Se-Met made 60%–75% of bound Se  Alkosel 500, Alkosel 1000, Selena, Lalmin Se1000, Lalmin Se2000, Alkosel 3000, Alkosel R397 Ruminants  Lallemand Inc.  Korhola, Vainio and Edelmann (1986)  Sour dough yeast  Candida milleri  ABM 4949  Alkomohr Biotech Ltd  Mäntynen et al. (1999)  Wine yeast  Low foaming, breeding of homothallic wine yeast strains  Pilot  Lallemand Inc.    Xylose yeast  Barley xylose isomerase cloned into distiller´s yeast (XI inactive)  Academic    Kristo et al. (1996)  Zinc-enriched yeast  Zn biologically bound  Sinkkona, Lalmin Zn50, Servomyces  Lallemand Inc.    View Large Table 1. Products and processes developed. Product/process  Essential feature  Trade name/pilot/academic  Further developments  Reference  Amylolytic yeast  Hormoconis resinae glucoamylase P gene expressed  Academic      Baker’s yeast  High rate of fermentation in lean/sugar dough; classical breeding  LaFlorida  Acidos Organicos SA, Tlalnepantla, Mexico    Brewer’s yeast  Old-fashioned lager Pof—yeast, craft beer yeast  ABM 1326  Alkomohr Biotech Ltd, Helsinki, Finland    Chromium-enriched yeast  Cr biologically bound  Kromona, Lalmin Cr2000  Lallemand Inc., Montreal, Canada    Distiller’s yeast  Ethanol tolerance improved  ALKO 554  Alko Ltd, Helsinki, Finland  Korhola (2010)  Enzymatic fuel cell  Bacterial PQQ-methanol dehydrogenase product application  Pilot  Enfucell Ltd, Vantaa, Finland  US Pat 7384701  Folate yeasts  Folates (Vitamin B9)  Academic    Korhola et al. (2014)  Glutathione yeast  Especially high GSH content  Pilot phase  Lallemand Inc.    Industrial enzymes  Trichoderma reesei genetically engineered production platform  Biotouch, Econase, Ecopulp, Ecostone, Finase, Flashzyme  ROAL/AB Enzymes/ABF Ingredients Ltd, London, UK  Aho et al. (1991); US Pat 5665585  MEL yeasts  Alfa-Galactosidase, MEL genes  AGAL, Rokkaasi (pilot) MEL yeasts (pilot, academic)  Alkomohr Biotech Ltd  Liljeström-Suominen, Joutsjoki and Korhola (1988); US Pat 5055401  Selenium-enriched yeast  Se biologically bound in place of sulfur. L-Se-Met made 60%–75% of bound Se  Alkosel 500, Alkosel 1000, Selena, Lalmin Se1000, Lalmin Se2000, Alkosel 3000, Alkosel R397 Ruminants  Lallemand Inc.  Korhola, Vainio and Edelmann (1986)  Sour dough yeast  Candida milleri  ABM 4949  Alkomohr Biotech Ltd  Mäntynen et al. (1999)  Wine yeast  Low foaming, breeding of homothallic wine yeast strains  Pilot  Lallemand Inc.    Xylose yeast  Barley xylose isomerase cloned into distiller´s yeast (XI inactive)  Academic    Kristo et al. (1996)  Zinc-enriched yeast  Zn biologically bound  Sinkkona, Lalmin Zn50, Servomyces  Lallemand Inc.    Product/process  Essential feature  Trade name/pilot/academic  Further developments  Reference  Amylolytic yeast  Hormoconis resinae glucoamylase P gene expressed  Academic      Baker’s yeast  High rate of fermentation in lean/sugar dough; classical breeding  LaFlorida  Acidos Organicos SA, Tlalnepantla, Mexico    Brewer’s yeast  Old-fashioned lager Pof—yeast, craft beer yeast  ABM 1326  Alkomohr Biotech Ltd, Helsinki, Finland    Chromium-enriched yeast  Cr biologically bound  Kromona, Lalmin Cr2000  Lallemand Inc., Montreal, Canada    Distiller’s yeast  Ethanol tolerance improved  ALKO 554  Alko Ltd, Helsinki, Finland  Korhola (2010)  Enzymatic fuel cell  Bacterial PQQ-methanol dehydrogenase product application  Pilot  Enfucell Ltd, Vantaa, Finland  US Pat 7384701  Folate yeasts  Folates (Vitamin B9)  Academic    Korhola et al. (2014)  Glutathione yeast  Especially high GSH content  Pilot phase  Lallemand Inc.    Industrial enzymes  Trichoderma reesei genetically engineered production platform  Biotouch, Econase, Ecopulp, Ecostone, Finase, Flashzyme  ROAL/AB Enzymes/ABF Ingredients Ltd, London, UK  Aho et al. (1991); US Pat 5665585  MEL yeasts  Alfa-Galactosidase, MEL genes  AGAL, Rokkaasi (pilot) MEL yeasts (pilot, academic)  Alkomohr Biotech Ltd  Liljeström-Suominen, Joutsjoki and Korhola (1988); US Pat 5055401  Selenium-enriched yeast  Se biologically bound in place of sulfur. L-Se-Met made 60%–75% of bound Se  Alkosel 500, Alkosel 1000, Selena, Lalmin Se1000, Lalmin Se2000, Alkosel 3000, Alkosel R397 Ruminants  Lallemand Inc.  Korhola, Vainio and Edelmann (1986)  Sour dough yeast  Candida milleri  ABM 4949  Alkomohr Biotech Ltd  Mäntynen et al. (1999)  Wine yeast  Low foaming, breeding of homothallic wine yeast strains  Pilot  Lallemand Inc.    Xylose yeast  Barley xylose isomerase cloned into distiller´s yeast (XI inactive)  Academic    Kristo et al. (1996)  Zinc-enriched yeast  Zn biologically bound  Sinkkona, Lalmin Zn50, Servomyces  Lallemand Inc.    View Large SELENIUM-ENRICHED YEAST—WE RETURNED WHAT THE GLACIERS TOOK AWAY My first project at ALKO was selenium yeast. Soil in Finland is poor in minerals because receding glaciers of the ice age scraped off most of the soil. There was governmental and public concern as well as concrete data showing that Finns’ diets were deficient in the anti-oxidant selenium. Some not very good selenium-containing products were available; mostly selenium salts mixed with organic carrier, or inactive dried yeast. Dr Oura asked me whether and how difficult it would be to produce an ‘organic’ yeast that incorporated selenium in place of sulfur via its normal metabolism? To test for organically bound selenium, we simply extracted test yeast with hot water or dilute acid (10% HCl). Non-extractable selenium was considered organically bound and extractable the inorganic salt. Using this assay, we developed the analytical procedures and industrial production process needed to produce yeast that incorporated 1000 mg of selenium per kg of dry product. Most of the incorporated selenium was L-selenomethionine with only a few % as inorganic selenium salt (Korhola, Vainio and Edelmann 1986; Table 1). Alko marketed the selenium yeast products under trade names ALKOSEL 500 and 1000 for animal feed and SELENA 100 for human consumption (by Huhtamäki/Leiras). Using our experience with selenium-enriched yeast products, we also developed zinc- and chromium-enriched supplements, Alko Sinkkona and Kromona, respectively (Table 1). After Alko Ltd. was split up into three companies in 1995, these yeast products were sold to Lallemand Inc., Montreal, Canada. They continued to further develop and market them as Alkosel 3000 and R397 for ruminants and Lalmin Se1000, 2000, Lalmin Zn50 and Lalmin Cr2000 for humans. Hence, my first yeast project developed into a multimillion dollar business. ETHANOL TOLERANCE AND CASCADE FERMENTATION—ETHANOL PRODUCTION ON A WORLD SCALE One of the basic problems in translating scientific results into industrial reality is the tendency of scientists faced with commercial opportunities to overextend real characterizations of their discoveries to imaginary ‘best of all possible worlds’ levels—a description of how things would be if all conceivable problems were solved. Such rosy characterizations lead engineers to expect that a technological and practical revolution is just around the corner. But usually it isn’t. I acquired first-hand experience with the hope vs reality thing in another of my early projects. I optimistically began with baker's yeast strain ALKO 743, also used as our main distiller's yeast, and selected—by continuous culture under increasing ethanol pressure—a more ethanol-tolerant distiller’s yeast, ALKO 554 (MK 392; Table 1). Even though its fermentation characteristics were 20% better than its parent, our plant managers were just not impressed. My prized yeast strain failed to generate the revolution I had hoped for. Adding insult to injury, our yeast production factory, which grew the yeast biomass, started charging the alcohol fermentation plants a higher price for this specialty yeast. Consequently, a number of years later the fermentation plants returned to the old practice of using regular baker’s yeast. In 2015 at ISSY32 in Perugia, Italy, Dr Charles Abbas, Director of Yeast and Renewables Research for the Archer Daniels Midland Company (ADM) made a presentation describing their grain fuel alcohol production program. It is the world’s largest and uses cascade fermentation for continuous alcohol production. Cascade fermentation begins with a line of many tanks. Saccharified starting medium is pumped into the first fermentation tank with the fully fermented broth exiting from the last tank for distillation and fodder separation. He told me the ADM alcohol plant managers called it ‘The Finnish Cascade’ when he joined the company in 1989. That may have been because the first cascade fermentation plant using grain raw material was invented and set up in mid-1980s at Alko’s expanded Koskenkorva barley grain alcohol fermentation plant. I participated in alcohol fermentation process development by establishing realistic ethanol production parameters using experimental values derived from continuous culture fermentation (Korhola 2010). Plant engineers then used these values to calculate and establish fermentation process parameters from the yeast's point of view. Later the discovery of A-stat by Dr Toomas Paalme from Tallinn Technical University, Estonia, diminished the time required for these continuous culture determinations without sacrificing their accuracy. We used this method to study fermentation and growth characteristics of ALKO 743. We further cloned the fungal glucoamylase and barley xylose isomerase genes (Kristo et al.1996) to construct novel distiller’s yeasts for amylolytic and pentose fermentations, respectively (Table 1). The amylolytic yeast has enjoyed great potential, as recently shown by Mascoma/Lallemand on a large industrial scale. Some projects are huge successes, others not so much. The xylose isomerase expressed in yeast was inactive as are almost all similar enzymes. Industrial projects, however, are time sensitive and time on this one ran out. There was no chance to investigate the problem further and it remains one today. Pentose fermentation on an industrial scale has yet to be solved despite intermittent promising breakthroughs. MEL YEASTS—PUTTING WASTES TO WORK As occurs with many industrial projects, our work on the α-galactosidase or melibiase producing yeasts was motivated by a practical problem. Increased production capability can also mean increased waste disposal. Expanding our baker's yeast production facility created an effluent stream that exceeded the capacity of our waste treatment plant to process it. The problem is too much oxygen-consuming material in the yeast plant effluent. One culprit in the effluent was the sugar melibiose left over from raffinose metabolism in beet molasses. Normal yeast can’t metabolize it. Moreover, if we could develop a yeast that utilized melibiose, this waste product would increase our biomass yield by 1%–2%. Small increases translate to big profits in large-scale operations. Therefore, using rDNA techniques, we inserted the MEL1 gene encoding α-galactosidase into our baker´s yeast strain ALKO 743 which now effectively degraded melibiose. The strain performed as predicted and was patented (Liljeström-Suominen, Joutsjoki and Korhola 1988; Table 1). However, further development and commercial use of this success encountered the unfavorable politics of GMO (genetically modified organisms). To this day, GMO antagonism and regulations prevent the use of GMO baker´s yeasts. Other commercially useful constructs that we engineered met the same fate and had to be abandoned. However, the MEL project was a good learning experience for the new personnel and prepared us to launch into engineering a tailored industrial enzyme production strain platform from the fungus Trichoderma reesei. A SHELFED PROJECT FINDS A NEW FRIEND Although commercialization of the MEL yeast strain ended, the scientific project itself continued and was even expanded after Dr Gennadi I. Naumov from Moscow came to visit (Fig. 2, right). During our first dinner together, I realized that he was a real scientist deeply interested in fermentation gene families and genetic taxonomy. This was refreshing because my earlier experience with official projects involving Soviet scientists was somewhat discouraging. The heads of institutes or departments permitted to interact with us seemed to be more like ‘political scientists’. Dr Naumov and his wife Dr Elena S. Naumova collaborated with us several times both in my lab at Alko and at the University of Helsinki to analyze and map the different S. cerevisiae MEL genes. Interestingly, the 12 MEL genes are located on different chromosomes about 30 kb from the telomeres in the subtelomeric regions (Fig. 4, top). Our most cited paper (Naumov et al.1992) describes genetic homologies of the species S. cerevisiae, S. bayanus and S. paradoxus. Together with Prof. Tahia Benitez from Seville, Spain, we used the same molecular probes to compare chromosomal polymorphism and adaptation of baker’s and distiller’s yeasts to environmental conditions. A paper on chromosomal reorganization during meiosis of S. cerevisiae baker’s yeast demonstrated unexpectedly large karyotypic changes, probably caused by mobilization of transposons. At that time the accepted view was that chromosomes are quite stable—plasticity of chromosomes was only amply documented after enough whole genome DNA sequence data had been accumulated. Success of these projects depended heavily on valuable molecular probes provided by Prof. Peter Philippsen (Fig. 1). Figure 4. View largeDownload slide Top: The S. cerevisiae α-galactosidase MEL gene family identified and studied at the author´s laboratory plus MEL12 (G. Naumov, personal communication). (Artwork, Edvard Partti). Bottom: Sour dough yeast researchers in 2003: Prof. Hannu Salovaara, Dr Haruhiko Mori, Andersen Service Co., Japan, and the author Matti Korhola. Figure 4. View largeDownload slide Top: The S. cerevisiae α-galactosidase MEL gene family identified and studied at the author´s laboratory plus MEL12 (G. Naumov, personal communication). (Artwork, Edvard Partti). Bottom: Sour dough yeast researchers in 2003: Prof. Hannu Salovaara, Dr Haruhiko Mori, Andersen Service Co., Japan, and the author Matti Korhola. SOUR DOUGH YEASTS AND PIZZA My interest in natural sour dough yeasts in Finnish rye bread started in 1980. Prof. Hannu Salovaara at the University of Helsinki and I started a long-term collaboration isolating and characterizing the yeasts (and lactic acid bacteria) from samples of domestic and commercial rye bread doughs (Fig. 4, bottom). The most prevalent wild yeasts in rye sour dough are Candida milleri, Torulaspora delbrueckii and added commercial baker's yeast (Mäntynen et al.1999; Table 1). Unfortunately, the first two yeasts cannot use maltose, the main sugar in the dough; they are Mal-negative. On the other hand, all three yeasts are able to utilize the sugars—glucose, fructose and sucrose—that make up ∼1%–3% of rye flour weight. I am currently investigating whether utilization of these three sugars is responsible for rye sour dough raising. There is also taxonomic interest in C. milleri. The issue, are C. humilis and C. milleri the same species? In the 1998 edition of the taxonomic treatise ‘The Yeasts’, Kurtzman united the two species as C. humilis based on sequence identity in the 25S rDNA D1/D2 region. However, he subsequently observed sufficient sequence diversity in four different protein coding genes to question that conclusion. We observed that all of the studied C. milleri strains have several SUC genes on different chromosomes as do many S. cerevisiae strains. We made a polyphasic taxonomic study of the relationships of industrial sour dough yeasts to other yeasts. In the latest 2011 edition of the ‘Yeasts’, the authors stated about the work of Mäntynen et al. (1999): ‘Unfortunately, authentic strains of C. humilis were not included in the study’. My explanation for the absence of C. humilis in the study was that C. milleri had already been named C. humilis—obviously we now have to re-examine this relationship. We also used sour dough yeasts to study folates (vitamin B9) made under fermentation conditions (Korhola et al.2014; Table 1). Brewer’s yeasts, together with lactic acid bacteria, are sometimes used to add a sour dough aroma to pizza crust. Interestingly, our brewer’s yeast has only been used for making beer on a small commercial scale (Table 1). SLONIMSKI—‘MATTI, YOU’RE IT’ In 1982, Dr Eriksson established and asked me to lead the Foundation for Biotechnical and Industrial Fermentation Research which awarded research grants from funds annually provided by Alko Ltd, ∼1 M euro in today’s money. I organized yeast symposia as part of our research activities and the Foundation published the proceedings. I happened to invite a number of younger well-known yeast scientists to our first such symposium, ‘Gene Expression in Yeast’ (Fig. 1). Three of those speakers went on to become Nobel Laureates: Jack W. Szostak in 2009 for his work on yeast telomeres and the enzyme telomerase, Randy W. Schekman in 2013 for his work on genetics of yeast vesicular traffic, i.e. the cell’s protein transport system and Michael Rosbash in 2017 for his work on the mechanisms controlling the circadian clock. At the banquet of the 1984 Edinburgh 12th International Conference on Yeast Genetics and Molecular Biology, the ‘Pope’, Piotr Slonimski, suddenly asked me whether I would be willing to organize the 1988 Conference (Fig. 5, top). That conference, the 14th International Conference on Yeast Genetics and Molecular Biology (ICYGMB), was attended by 717 registered participants, a record at that time. That conference also represented my entry into the Finance and Policy Committee of ICYGMB which selects the venues for future conferences. From 1983 onwards, I have also been a Finnish representative to the International Commission on Yeasts which makes decisions about future International Specialized Symposia on Yeasts and the International Congresses on Yeasts. I have always felt at ease both in molecular biology and traditional yeast circles—yeasts are so interesting and the research rewarding. Figure 5. View largeDownload slide Top: Prof. Piotr Slonimski demonstrating with a mushroom a point mutation in the mitochondrial gene BOX2. There was a dispute between the American and French schools of mitochondrial researchers on naming the apocytochrome b gene. The compromise was to call it cob-box. We found evidence also for BOX6, and BOX8 on our way to the nature reserve of Alko Ltd in Raasepori, Finland in 1981. Today the accepted name is COB and the systematic name, Q0105. The name ‘box’ was retained in the ´box effect´, i.e. many mutations in the COB gene introns that prevent the synthesis of cytochrome b and cytochrome oxidase subunit I. Bottom: Key personnel of Alkomohr Biotech Ltd in 1999. From left to right: Dr Hilkka Turakainen, Dr Matti Korhola, Dr Vesa Mäntynen and M.Sc. Marja Aittamaa. We are sniffing and evaluating new wine yeast genetic hybrids made by Aittamaa using spore-to-spore crossing of the homothallic starting strains. Figure 5. View largeDownload slide Top: Prof. Piotr Slonimski demonstrating with a mushroom a point mutation in the mitochondrial gene BOX2. There was a dispute between the American and French schools of mitochondrial researchers on naming the apocytochrome b gene. The compromise was to call it cob-box. We found evidence also for BOX6, and BOX8 on our way to the nature reserve of Alko Ltd in Raasepori, Finland in 1981. Today the accepted name is COB and the systematic name, Q0105. The name ‘box’ was retained in the ´box effect´, i.e. many mutations in the COB gene introns that prevent the synthesis of cytochrome b and cytochrome oxidase subunit I. Bottom: Key personnel of Alkomohr Biotech Ltd in 1999. From left to right: Dr Hilkka Turakainen, Dr Matti Korhola, Dr Vesa Mäntynen and M.Sc. Marja Aittamaa. We are sniffing and evaluating new wine yeast genetic hybrids made by Aittamaa using spore-to-spore crossing of the homothallic starting strains. INDUSTRY—IT’S THE EUROPEAN COMMISSION CALLING One of the highlights in my career occurred in a large negotiation room of the European Commission Berlaymont building in Brussels, Belgium. At this large 1989 meeting on EU research programs, one of the questions raised was whether yeast-related industries would form a consortium to support EU programs. The European Commission wanted an industry response to and participation in the megaprojects it was planning, including whole genome sequencing of S. cerevisiae. Among its initial pilot projects was the sequencing of S. cerevisiae chromosome III. Suddenly, at the end of that meeting, I found myself surrounded by about 20 attendees who drafted me to become Chairman for the yeast industry's activities. In answer to the Commission, the European yeast and yeast-related industries formally established the Yeast Industry Platform (YIP) which committed itself to support and exploit European yeast research, develop a European regulatory framework in biotechnology and provide objective information on yeast-related biotechnology to the general public. The member companies of YIP were represented by their research directors and other influential yeast scientists (Table 2). YIP representatives attended all of the yeast sequencing progress meetings where leading edge information and yeast genomics were presented and discussed. We, as industrial representatives, were warmly received as joint partners with academic scientists in the S. cerevisiae genome sequencing project and its continuation as EUROFAN (European Functional Analysis Network of Unknown Yeast Genes). Table 2. Members of the YIP at the time of its foundation in 1991 (modified from the book: Goujon P. From Biotechnology to Genomes. The Meaning of the Double Helix. Singapore: World Scientific, 2001). Company  Activity  Representative  Alko Ltd, Helsinki, FI  Alcoholic beverages, baker’s yeast, industrial enzymes  Dr Matti Korhola, Director of the Research Laboratories, Director of YIP  Boehringer Mannheim GmbH, DE  Pharmaceuticals and biochemicals  Dr Werner Wolf, Vice President R&D  Champagne Moet & Chandon, Épernay, FR  Alcoholic beverages  Dr Bruno Duteurtre  Interbrew NV, Leuven, BE  Beer  Dr Dirk Iserentant  KabiVitrum AB, Uppsala, SE  Peptide hormones, pharmaceuticals and biochemicals  Dr Linda Fryklund  LeSaffre et Cie, Marcq-en-Baroeul, FR  Baker´s, beer, distiller´s and wine yeasts  Philippe Clement  Nestec Ltd, Vevey, SW  R&D for Nestle food and drink  Dr Peter Niederberger  Pernod Ricard SA, Creteil, FR  Alcoholic beverages  Dr Barbu Vladescu  Rhone Poulenc Rorer SA, Anthony, FR  Pharmaceuticals  Dr Reinhard Fleer  Royal Gist Brocades NV, Delft, NL  Yeast, industrial and pharmaceutical enzymes  Dr Klaus Osinga  Tepral BSN Drinks Research Centre, Strasbourg, FR  Beer, champagne, bread  Dr Frédéric Gendre  Transgene SA, Strasbourg, FR  Research contracts  Dr R. Gloecker  Unilever NV, Vlaardingen, NL  Foods, specialty chemicals, beer  Dr John M.A. Verbakel  Company  Activity  Representative  Alko Ltd, Helsinki, FI  Alcoholic beverages, baker’s yeast, industrial enzymes  Dr Matti Korhola, Director of the Research Laboratories, Director of YIP  Boehringer Mannheim GmbH, DE  Pharmaceuticals and biochemicals  Dr Werner Wolf, Vice President R&D  Champagne Moet & Chandon, Épernay, FR  Alcoholic beverages  Dr Bruno Duteurtre  Interbrew NV, Leuven, BE  Beer  Dr Dirk Iserentant  KabiVitrum AB, Uppsala, SE  Peptide hormones, pharmaceuticals and biochemicals  Dr Linda Fryklund  LeSaffre et Cie, Marcq-en-Baroeul, FR  Baker´s, beer, distiller´s and wine yeasts  Philippe Clement  Nestec Ltd, Vevey, SW  R&D for Nestle food and drink  Dr Peter Niederberger  Pernod Ricard SA, Creteil, FR  Alcoholic beverages  Dr Barbu Vladescu  Rhone Poulenc Rorer SA, Anthony, FR  Pharmaceuticals  Dr Reinhard Fleer  Royal Gist Brocades NV, Delft, NL  Yeast, industrial and pharmaceutical enzymes  Dr Klaus Osinga  Tepral BSN Drinks Research Centre, Strasbourg, FR  Beer, champagne, bread  Dr Frédéric Gendre  Transgene SA, Strasbourg, FR  Research contracts  Dr R. Gloecker  Unilever NV, Vlaardingen, NL  Foods, specialty chemicals, beer  Dr John M.A. Verbakel  View Large Table 2. Members of the YIP at the time of its foundation in 1991 (modified from the book: Goujon P. From Biotechnology to Genomes. The Meaning of the Double Helix. Singapore: World Scientific, 2001). Company  Activity  Representative  Alko Ltd, Helsinki, FI  Alcoholic beverages, baker’s yeast, industrial enzymes  Dr Matti Korhola, Director of the Research Laboratories, Director of YIP  Boehringer Mannheim GmbH, DE  Pharmaceuticals and biochemicals  Dr Werner Wolf, Vice President R&D  Champagne Moet & Chandon, Épernay, FR  Alcoholic beverages  Dr Bruno Duteurtre  Interbrew NV, Leuven, BE  Beer  Dr Dirk Iserentant  KabiVitrum AB, Uppsala, SE  Peptide hormones, pharmaceuticals and biochemicals  Dr Linda Fryklund  LeSaffre et Cie, Marcq-en-Baroeul, FR  Baker´s, beer, distiller´s and wine yeasts  Philippe Clement  Nestec Ltd, Vevey, SW  R&D for Nestle food and drink  Dr Peter Niederberger  Pernod Ricard SA, Creteil, FR  Alcoholic beverages  Dr Barbu Vladescu  Rhone Poulenc Rorer SA, Anthony, FR  Pharmaceuticals  Dr Reinhard Fleer  Royal Gist Brocades NV, Delft, NL  Yeast, industrial and pharmaceutical enzymes  Dr Klaus Osinga  Tepral BSN Drinks Research Centre, Strasbourg, FR  Beer, champagne, bread  Dr Frédéric Gendre  Transgene SA, Strasbourg, FR  Research contracts  Dr R. Gloecker  Unilever NV, Vlaardingen, NL  Foods, specialty chemicals, beer  Dr John M.A. Verbakel  Company  Activity  Representative  Alko Ltd, Helsinki, FI  Alcoholic beverages, baker’s yeast, industrial enzymes  Dr Matti Korhola, Director of the Research Laboratories, Director of YIP  Boehringer Mannheim GmbH, DE  Pharmaceuticals and biochemicals  Dr Werner Wolf, Vice President R&D  Champagne Moet & Chandon, Épernay, FR  Alcoholic beverages  Dr Bruno Duteurtre  Interbrew NV, Leuven, BE  Beer  Dr Dirk Iserentant  KabiVitrum AB, Uppsala, SE  Peptide hormones, pharmaceuticals and biochemicals  Dr Linda Fryklund  LeSaffre et Cie, Marcq-en-Baroeul, FR  Baker´s, beer, distiller´s and wine yeasts  Philippe Clement  Nestec Ltd, Vevey, SW  R&D for Nestle food and drink  Dr Peter Niederberger  Pernod Ricard SA, Creteil, FR  Alcoholic beverages  Dr Barbu Vladescu  Rhone Poulenc Rorer SA, Anthony, FR  Pharmaceuticals  Dr Reinhard Fleer  Royal Gist Brocades NV, Delft, NL  Yeast, industrial and pharmaceutical enzymes  Dr Klaus Osinga  Tepral BSN Drinks Research Centre, Strasbourg, FR  Beer, champagne, bread  Dr Frédéric Gendre  Transgene SA, Strasbourg, FR  Research contracts  Dr R. Gloecker  Unilever NV, Vlaardingen, NL  Foods, specialty chemicals, beer  Dr John M.A. Verbakel  View Large FROM THEIR COMPANY TO MINE I resigned from YIP after Alko was split into three companies and the Research Laboratories were closed at the end of 1994. The following year I moved to the University of Helsinki and established my own company Alkomohr Biotech Ltd (Fig. 5, bottom). The name Alkomohr derived from an anagram, Matti Korhola: Alko pointing to my previous career at Alko Ltd and Mohr is also a West-African gazelle with graceful ringed horns. Our company slogan is ‘Yeast Improves Spirits’. Parenthetically, words and language have been a long-term interest of mine and led me to participate in publishing three editions of the Dictionary of Microbiology containing terms and definitions in Finnish, English and Swedish and to coin the name Enfucell for Enzymatic Fuel Cell. Alkomohr participated in the first phase of EUROFAN, working on six genes. We also pursued commercial product development projects: constructing new baker’s and wine yeast strains, as well as developing our own α-galactosidase and methanol dehydrogenase products (Table 1). I also started consulting for Lallemand Inc. on scientific and product development matters, and represented them in YIP from 1999 to 2001 (Fig. 6). However, during my absence from YIP between 1994 and 1999—and to my dissatisfaction—YIP slipped into focusing more on socioeconomic issues than concentrating on yeast science and applications. Gradually, YIP faded away in 2002 (Table 2). Figure 6. View largeDownload slide Participating in the 2002 VH Yeast Days ‘Advances in Science and Industrial Production of Baker´s Yeast’ in Dresden, Germany. From left: the author Matti Korhola, Dr Richard Degré Vice President RD/QA Lallemand and Erkki Varonen Plant Manager Finnish Yeast/Lallemand. Figure 6. View largeDownload slide Participating in the 2002 VH Yeast Days ‘Advances in Science and Industrial Production of Baker´s Yeast’ in Dresden, Germany. From left: the author Matti Korhola, Dr Richard Degré Vice President RD/QA Lallemand and Erkki Varonen Plant Manager Finnish Yeast/Lallemand. FRIENDS TO NO FRIENDS AND BACK During the second phase of EUROFAN, I participated from a new vantage point as one of the EU Commission project evaluators. Many of the large European labs participated in that phase, which was a worldwide effort to characterize the remaining S. cerevisiae genes whose functions were still unknown. We received a total of ∼12 M euro in requests, for which the Commission had budgeted only 8 M euro. Not surprisingly, some of the individual projects had to be eliminated to avoid the alternative cheese slicing and dicing. As a result, I received a frosty welcome at the next EUROFAN meeting in Manchester, UK—few even ‘saw me’ or shook hands. However, by the following meeting all appeared to be forgiven and we were friends again. Despite this dedicated effort, there are still today ∼10% or 600 genes of unknown function in yeast. WE MAKE’EM TO ORDER Our first foray into tailor-made enzyme production strains occurred when Alko Ltd sought to expand into the international industrial enzyme business. The company had for many years been producing Aspergillus glucoamylase and Bacillus α-amylase for use in its grain alcohol fermentation plants. With yeast experience under our belts, we turned our attention to strain construction projects for the production of industrial grade enzymes. It was here in 1983 that I formulated the principles for and devised the concept of tailor-made production strains: cloning and overexpression of desired genes and inactivation of deleterious genes for a given application (Table 1). The largest scale industrial enzymes, α-amylases, glucoamylases, cellulases, hemicellulases, pectinases and proteases, are all secreted and hence we had to cope with few deleterious genes. Traditionally, the marketed products were individual, concentrated, growth-culture supernatants. The final product was then formulated by mixing appropriate amounts of two or more of these enzyme concentrates to yield the desired salable product. In contrast, our approach was to let nature do the ‘mixing’ by molecular tailoring of the production organism. Of course, the traditional mixing approach was still available, but our approach surprised and impressed market leaders. Our first success was production of Bacillus subtilis containing α-amylase. Here a Finnish group funded by SITRA cloned the α-amylase gene from Alko´s production strain B. amyloliquefaciens. That was the easy part. The more difficult challenge was to win approval from government officials for full-scale factory production. In surmounting that challenge, we taught a 2-week course on microbiology and rDNA technologies at the factory and changed some of our effluent handling procedures. Our initial 60 m3 full-scale production was probably the first recombinant industrial enzyme product used for starch liquefaction in grain alcohol fermentation. We next tailored fungi, first inducing and selecting mutations in our glucoamylase production strain Aspergillus awamori. This strain produced large amounts of protease(s) in addition to glucoamylase. The mutagenesis and selection work confirmed the feasibility of altering the ratios of secreted enzymes without affecting the desired activity. COURT CASE FAILED, BUT COLLABORATION DIDN’T The market leader in industrial enzymes, Novo Nordisk (later Novozymes), learned of our new venture because they had occasionally supplied α- and glucoamylases for our fermentation plant. This caused them consternation to the point that they tried to block our efforts by presenting us with an irresistible offer, selling us those two enzymes below our own production costs. To no avail. We continued developing our fungal production organism platform, T. reesei, in collaboration with VTT where we funded their fungal group. Here yeast was used only as a tool for specific steps in the development work (Table 1; Aho et al.1991). Of course, we patented our inventions, leading Novozymes to attack us in court, a case they finally lost in 2008. In the meanwhile, Genencor, ROAL + AB Enzymes (successors of the Alko-Röhm joint venture), and Novozymes consumated cross-licensing deals permitting all three companies to use the Trichoderma platform for their enzyme production. In this way Trichoderma has now joined Aspergillus as an important platform for industrial fungal enzyme production with ROAL, supporting ∼150 employees and 60 M euro in receipts. Although the market value of industrial enzymes for ABF Ingredients is undisclosed, it is likely several fold greater than the factory price just mentioned. BIG DATA VS YEAST—YEAST WINS The latest revolution in microbial research has been the application of ‘omics’ technologies, i.e. genomics, transcriptomics, proteomics, lipidomics and metabolomics, in microbial strain and population studies. This has generated `big data`, the interpretation of which presently seems to be based on homologies to already known structural and functional entities. This new approach is offering immense opportunities to increase our understanding of cellular functions at a more comprehensive and detailed level than ever before. However, for industrial strain construction this approach still has some way to go. The genomes of some of my mutants (Table 1), intended for industrial use, have been fully sequenced with the goal of understanding the ‘whole big picture’. Thus far, with limited success. The expertise to fully utilize ‘big data’ is still limited. Realization of the gold standard, interpreting ‘big data’ in terms of yeast physiology that is industrially relevant, remains only on the horizon. Acknowledgements I want to thank Mr. Jean Chagnon, the owner, and Dr Richard Degré, Vice President R&D/QA, both of Lallemand Inc., Montreal, Canada for the visionary place for 15 years in their organization allowing me to observe and contribute to the growth of their company into one of the three world leaders in yeast business. I also thank Terry Cooper for thorough editing of the manuscript for increased reader friendliness. Conflict of interest. None declared. REFERENCES Aho S, Olkkonen V, Jalava T et al.   Monoclonal antibodies against core and cellulose-binding domains of Trichoderma reesei cellobiohydrolases I and II and endoglucanase I. Eur J Biochem  1991; 200: 643– 9. Google Scholar CrossRef Search ADS PubMed  Kristo P, Saarelainen R, Aho S et al.   Protein purification, and cloning and characterization of the cDNA and gene for xylose isomerase of barley. Eur J Biochem  1996; 237: 240– 6. Google Scholar CrossRef Search ADS PubMed  Korhola M. Developments in vodka production. In: Walker GM, Hughes PS (eds). Distilled Spirits – New Horizons: Energy, Environment and Enlightenment . Nottingham: Nottingham University Press, 2010, 53– 61. Google Scholar CrossRef Search ADS   Korhola M, Hakonen R, Juuti K et al.   Production of folate in oat bran fermentation by yeasts isolated from barley and diverse foods. J Appl Microbiol  2014; 117: 679– 89. Google Scholar CrossRef Search ADS PubMed  Korhola M, Vainio A, Edelmann K. Selenium yeast. Ann Clin Res  1986; 18: 65– 68. Google Scholar PubMed  Liljeström-Suominen PL, Joutsjoki V, Korhola M. Construction of a stable α-galactosidase-producing baker's yeast strain. Appl Environm Microb  1988; 54: 245– 9. Mäntynen VH, Korhola M, Gudmundsson H et al.   A polyphasic study on the taxonomic position of industrial sour dough yeasts. System and Appl Microbiol  1999; 22: 87– 96. Google Scholar CrossRef Search ADS   Naumov GI, Naumova ES, Lantto RA et al.   Genetic homology between Saccharomyces cerevisiae and its sibling species S. paradoxus and S. bayanus: Electrophoretic karyotypes. Yeast  1992; 8: 599– 612. Google Scholar CrossRef Search ADS PubMed  © FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
TI - Between science and industry—applied yeast research
JF - FEMS Yeast Research
DO - 10.1093/femsyr/foy008
DA - 2018-03-01
UR - https://www.deepdyve.com/lp/oxford-university-press/between-science-and-industry-applied-yeast-research-fkAhnFa7Rc
SP - foy008
VL - 18
IS - 2
DP - DeepDyve
ER -