title: Improving the productivity of S-adenosyl-l-methionine by metabolic engineering in an industrial Saccharomyces cerevisiae strain.
abstract: S-Adenosyl-l-methionine (SAM) is an important metabolite having prominent roles in treating various diseases. In order to improve the production of SAM, the regulation of three metabolic pathways involved in SAM biosynthesis were investigated in an industrial yeast strain ZJU001. GLC3 encoded glycogen-branching enzyme (GBE), SPE2 encoded SAM decarboxylase, as well as ERG4 and ERG6 encoded key enzymes in ergosterol biosynthesis, were knocked out in ZJU001 accordingly. The results indicated that blocking of either glycogen pathway or SAM decarboxylation pathway could improve the SAM accumulation significantly in ZJU001, while single disruption of either ERG4 or ERG6 gene had no obvious effect on SAM production. Moreover, the double mutant ZJU001-GS with deletion of both GLC3 and SPE2 genes was also constructed, which showed further improvement of SAM accumulation. Finally, SAM2 was overexpressed in ZJU001-GS to give the best SAM-producing recombinant strain ZJU001-GS-SAM2, in which 12.47g/L SAM was produced by following our developed pseudo-exponential fed-batch cultivation strategy, about 81.0% increase comparing to its parent strain ZJU001. The present work laid a solid base for large-scale SAM production with the industrial Saccharomyces cerevisiae strain.
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Weijun
authors: W
authors: Zhao
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Baojian
authors: B
authors: Hang
authors: Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, Hunan, China. Electronic address: seanzhu1996@aliyun.com.
authors: Xiangcheng
authors: X
authors: Zhu
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Ri
authors: R
authors: Wang
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Minjie
authors: M
authors: Shen
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Lei
authors: L
authors: Huang
authors: Key laboratory of Biomass Chemical Engineering (Ministry of Education), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: znxu@zju.edu.cn.
authors: Zhinan
authors: Z
authors: Xu
mesh_terms: D005285:Fermentation; D007218:Industrial Microbiology; D060847:Metabolic Engineering / Q000379:methods*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D012436:S-Adenosylmethionine
keywords: GLC3; S-Adenosyl-l-methionine; SAM2; SPE2; Saccharomyces cerevisiae