title: Progress in the microbial production of S-adenosyl-L-methionine.
abstract: S-Adenosyl-L-methionine (SAM), which exists in all living organisms, serves as an activated group donor in a range of metabolic reactions, including trans-methylation, trans-sulfuration and trans-propylamine. Compared with its chemical synthesis and enzyme catalysis production, the microbial production of SAM is feasible for industrial applications. The current clinical demand for SAM is constantly increasing. Therefore, vast interest exists in engineering the SAM metabolism in cells for increasing product titers. Here, we provided an overview of updates on SAM microbial productivity improvements with an emphasis on various strategies that have been used to enhance SAM production based on increasing the precursor and co-factor availabilities in microbes. These strategies included the sections of SAM-producing microbes and their mutant screening, optimization of the fermentation process, and the metabolic engineering. The SAM-producing strains that were used extensively were Saccharomyces cerevisiae, Pichia pastoris, Candida utilis, Scheffersomyces stipitis, Kluyveromyces lactis, Kluyveromyces marxianus, Corynebacterium glutamicum, and Escherichia coli, in addition to others. The optimization of the fermentation process mainly focused on the enhancement of the methionine, ATP, and other co-factor levels through pulsed feeding as well as the optimization of nitrogen and carbon sources. Various metabolic engineering strategies using precise control of gene expression in engineered strains were also highlighted in the present review. In addition, some prospects on SAM microbial production were discussed.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: Zhilai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Cai
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, Jiangsu, People's Republic of China. cl_zhou@cpu.edu.cn.
authors.forename: Changlin
authors.initials: C
authors.lastname: Zhou
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000254:growth & development; D053898:Biosynthetic Pathways; D005285:Fermentation; D005658:Fungi / Q000235:genetics* / Q000254:growth & development; D005798:Genes, Bacterial; D005800:Genes, Fungal; D060847:Metabolic Engineering / Q000379:methods*; D009154:Mutation; D012436:S-Adenosylmethionine / Q000378:metabolism*
chemical_list: D012436:S-Adenosylmethionine
keywords: Conventional strain breeding; Fermentation process; Metabolic engineering; Microbial production; Mutant screening; S-Adenosyl-L-methionine