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

Wenping Xie, Lidan Ye, Xiaomei Lv, Haoming Xu, Hongwei Yu

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

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 1156. mg/L (20.79. mg/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.

Original languageEnglish
Pages (from-to)8-18
Number of pages11
JournalMetabolic Engineering
Volume28
DOIs
StatePublished - 1 Mar 2015
Externally publishedYes

Keywords

  • Biosynthetic pathway
  • Carotenoids
  • Metabolic engineering
  • Sequential control

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