Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae

Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates... Balanced utilization of metabolic intermediates and controllable expression of genes in biosynthetic pathways are key issues for the effective production of value-added chemicals in microbes. An inducer/repressor-free sequential control strategy regulated by glucose concentration in the growth environment was proposed to address these issues, and its efficiency was validated using heterologous beta-carotenoid biosynthesis in Saccharomyces cerevisiae as an example. Through sequential control of the downstream, upstream, and competitive pathways of farnesyl diphosphate (FPP), the crucial metabolic node in the biosynthesis of terpenoids, in a predetermined order, a carotenoid production of 1156mg/L (20.79mg/g DCW) was achieved by high-cell density fermentation. Quantitative PCR analysis of the regulated genes demonstrated that the transcription patterns were controlled in a sequential manner as expected. The inducer/repressor-free nature of this strategy offers a both practical and economically efficient approach to improved biosynthetic production of value-added chemicals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Metabolic Engineering Elsevier

Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae

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Publisher
Elsevier
Copyright
Copyright © 2014 International Metabolic Engineering Society
ISSN
1096-7176
eISSN
1096-7184
D.O.I.
10.1016/j.ymben.2014.11.007
Publisher site
See Article on Publisher Site

Abstract

Balanced utilization of metabolic intermediates and controllable expression of genes in biosynthetic pathways are key issues for the effective production of value-added chemicals in microbes. An inducer/repressor-free sequential control strategy regulated by glucose concentration in the growth environment was proposed to address these issues, and its efficiency was validated using heterologous beta-carotenoid biosynthesis in Saccharomyces cerevisiae as an example. Through sequential control of the downstream, upstream, and competitive pathways of farnesyl diphosphate (FPP), the crucial metabolic node in the biosynthesis of terpenoids, in a predetermined order, a carotenoid production of 1156mg/L (20.79mg/g DCW) was achieved by high-cell density fermentation. Quantitative PCR analysis of the regulated genes demonstrated that the transcription patterns were controlled in a sequential manner as expected. The inducer/repressor-free nature of this strategy offers a both practical and economically efficient approach to improved biosynthetic production of value-added chemicals.

Journal

Metabolic EngineeringElsevier

Published: Mar 1, 2015

References

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