title: The Improvement of SAM Accumulation by Integrating the Endogenous Methionine Adenosyltransferase Gene SAM2 in Genome of the Industrial Saccharomyces cerevisiae Strain.
abstract: S-Adenosyl-L-methionine (SAM) plays important roles in trans-methylation, trans-sulfuration, and polyamine synthesis in all living cells, and it is also an effective cure for liver disease, depressive syndromes, and osteoarthritis. The increased demands of SAM in pharmaceuticals industry have aroused lots of attempts to improve its production. In this study, a multiple-copy integrative plasmid pYMIKP-SAM2 was introduced into the chromosome of wild-type Saccharomyces cerevisiae strain ZJU001 to construct the recombined strain R1-ZJU001. Further studies showed that the recombinant yeast exhibited higher enzymatic activity of methionine adenosyltransferase and improved its SAM biosynthesis. With a three-phase fed-batch strategy in 15-liter bench-top fermentor, 8.81 g/L SAM was achieved after 52 h cultivation of R1-ZJU001, about 27.1 % increase over its parent strain ZJU001, whereas the SAM content was also improved from 64.6 mg/g DCW to 91.0 mg/g DCW. Our results shall provide insights into the metabolic engineering of SAM pathway in yeast for improved productivity of SAM and subsequent industrial applications.
authors.affiliation: Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Shandong Institute for Food and Drug Control, Jinan, 250101, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.affiliation: Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Hang
authors.affiliation: Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.affiliation: Key Laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China. znxu@zju.edu.cn.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D015825:Chromosomes, Fungal; D005285:Fermentation; D016681:Genome, Fungal; D008716:Methionine Adenosyltransferase / Q000235:genetics*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D012436:S-Adenosylmethionine; D008716:Methionine Adenosyltransferase
keywords: Biosynthesis; Methionine adenosyltransferase; S-Adenosyl-L-methionine (SAM); Saccharomyces cerevisiae; Three-phase fed-batch strategy