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

Autor: Dong C; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China., Schultz JC; Department of Chemical and Biomolecular Engineering, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA., Liu W; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China., Lian J; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310027, China. Electronic address: jzlian@zju.edu.cn., Huang L; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China., Xu Z; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China. Electronic address: znxu@zju.edu.cn., Zhao H; Department of Chemical and Biomolecular Engineering, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: zhao5@illinois.edu.
Jazyk: angličtina
Zdroj: Metabolic engineering [Metab Eng] 2021 Jul; Vol. 66, pp. 319-327. Date of Electronic Publication: 2021 Mar 10.
DOI: 10.1016/j.ymben.2021.03.005
Abstrakt: 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.
(Copyright © 2021 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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