Metabolic engineering of a Saccharomyces cerevisiae strain capable of simultaneously utilizing glucose and galactose to produce enantiopure (2R,3R)-butanediol

Jiazhang Lian, Ran Chao, Huimin Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

2,3-Butanediol (BDO) is an important chemical with broad industrial applications and can be naturally produced by many bacteria at high levels. However, the pathogenicity of these native producers is a major obstacle for large scale production. Here we report the engineering of an industrially friendly host, Saccharomyces cerevisiae, to produce BDO at high titer and yield. By inactivation of pyruvate decarboxylases (PDCs) followed by overexpression of MTH1 and adaptive evolution, the resultant yeast grew on glucose as the sole carbon source with ethanol production completely eliminated. Moreover, the pdc- strain consumed glucose and galactose simultaneously, which to our knowledge is unprecedented in S. cerevisiae strains. Subsequent introduction of a BDO biosynthetic pathway consisting of the cytosolic acetolactate synthase (cyto. ILV2), Bacillus subtilis acetolactate decarboxylase (Bs. AlsD), and the endogenous butanediol dehydrogenase (BDH1) resulted in the production of enantiopure (2R,3R)-butanediol (R-BDO). In shake flask fermentation, a yield over 70% of the theoretical value was achieved. Using fed-batch fermentation, more than 100. g/L R-BDO (1100. mM) was synthesized from a mixture of glucose and galactose, two major carbohydrate components in red algae. The high titer and yield of the enantiopure R-BDO produced as well as the ability to co-ferment glucose and galactose make our engineered yeast strain a superior host for cost-effective production of bio-based BDO from renewable resources.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalMetabolic Engineering
Volume23
DOIs
StatePublished - May 2014

Keywords

  • (2R,3R)-Butanediol
  • Glucose derepression
  • Metabolic engineering
  • Pyruvate decarboxylase
  • Sugar co-utilization

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Applied Microbiology and Biotechnology

Fingerprint Dive into the research topics of 'Metabolic engineering of a Saccharomyces cerevisiae strain capable of simultaneously utilizing glucose and galactose to produce enantiopure (2R,3R)-butanediol'. Together they form a unique fingerprint.

Cite this