TY - JOUR
T1 - Identification of novel metabolic engineering targets for S-adenosyl-L-methionine production in Saccharomyces cerevisiae via genome-scale engineering
AU - Dong, Chang
AU - Schultz, J. Carl
AU - Liu, Wei
AU - Lian, Jiazhang
AU - Huang, Lei
AU - Xu, Zhinan
AU - Zhao, Huimin
N1 - Publisher Copyright:
© 2021 International Metabolic Engineering Society
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - CRISPR
KW - Genome-scale engineering
KW - Industrial S. cerevisiae
KW - S-Adenosyl-L-methionine
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U2 - 10.1016/j.ymben.2021.03.005
DO - 10.1016/j.ymben.2021.03.005
M3 - Article
C2 - 33713797
AN - SCOPUS:85106585651
SN - 1096-7176
VL - 66
SP - 319
EP - 327
JO - Metabolic Engineering
JF - Metabolic Engineering
ER -