Strain improvement for enhanced production of S-adenosyl-L-methionine in Saccharomyces cerevisiae based on ethionine-resistance and SAM synthetase activity

Abstract

S-adenosyl-L-methionine (SAM) is an essential metabolite in all living cells, and which plays an important role in cellular functions such as methylation, sulfuration, and polyamine synthesis. The current study was carried out to obtain an industrial strain with overproduction of SAM. The wild-type strain, Saccharomyces cerevisiae CGMCC 1226, was subjected to successive mutagenic with ultraviolet irradiation (UV) coupled with ethionine-resistant screening procedure to achieve a rapid improvement of S-adenosyl-L-methionine production in Saccharomyces cerevisiae. A high SAM yield strain, designated as Saccharomyces cerevisiae CGMCC 2842, was successfully selected and exhibited higher SAM synthetase activity which was increased by 2.7-fold in comparison with the wild-type strain. Meanwhile, the production of SAM by Saccharomyces cerevisiae CGMCC 2842 in a 15-L fermentor reached 6.1 g/L after 36 h fed-batch fermentation and was increased by 4.3-fold. In addition, the ethionine-resistant genes of the mutant and wild-type strains were cloned, and analyses of nucleotide sequences suggested that the replacements of amino acid residues could be responsible for the ethionine-resistance.