Identification of novel metabolic engineering targets for S-adenosyl-L-methionine production in Saccharomyces cerevisiae via genome-scale engineering

Chang Dong, J. Carl Schultz, Wei Liu, Jiazhang Lian, Lei Huang, Zhinan Xu, Huimin Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

S-Adenosyl-L-methionine (SAM) is an important intracellular metabolite and widely used for treatment of various diseases. Although high level production of SAM had been achieved in yeast, novel metabolic engineering strategies are needed to further enhance SAM production for industrial applications. Here genome-scale engineering (GSE) was performed to identify new targets for SAM overproduction using the multi-functional genome-wide CRISPR (MAGIC) system, and the effects of these newly identified targets were further validated in industrial yeast strains. After 3 rounds of FACS screening and characterization, numerous novel targets for enhancing SAM production were identified. In addition, transcriptomic and metabolomic analyses were performed to investigate the molecular mechanisms for enhanced SAM accumulation. The best combination (upregulation of SNZ3, RFC4, and RPS18B) improved SAM productivity by 2.2-fold and 1.6-fold in laboratory and industrial yeast strains, respectively. Using GSE of laboratory yeast strains to guide industrial yeast strain engineering presents an effective approach to design microbial cell factories for industrial applications.

Original languageEnglish (US)
Pages (from-to)319-327
Number of pages9
JournalMetabolic Engineering
Volume66
DOIs
StatePublished - Jul 2021

Keywords

  • CRISPR
  • Genome-scale engineering
  • Industrial S. cerevisiae
  • S-Adenosyl-L-methionine

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Bioengineering
  • Biotechnology

Fingerprint

Dive into the research topics of 'Identification of novel metabolic engineering targets for S-adenosyl-L-methionine production in Saccharomyces cerevisiae via genome-scale engineering'. Together they form a unique fingerprint.

Cite this