Enhanced co-production of S-adenosylmethionine and glutathione by an ATP-oriented amino acid addition strategy

Effects of amino acids on co-production of S-adenosylmethionine (SAM) and glutathione (GSH) with Candida utilis CCTCC M 209298 were investigated. Both methionine and cysteine showed positive effects on improving intracellular SAM and GSH content simultaneously. Batch fermentative co-production of SAM and GSH was conducted in a 5 L stirred fermentor, where the co-production of SAM and GSH was enhanced by 71.3% and 71.5% with 6 g/L methionine and 6 mmol/L cysteine, respectively. Based on these results together with intracellular ATP levels during batch cultivation of C. utilis CCTCC M 209298, a two-stage amino acid addition strategy was developed by adding 6 g/L methionine at 0 h and 6 mmol/L cysteine at 21 h. Under this ATP-oriented strategy, SAM and GSH biosynthesis was further promoted, and the co-production of SAM and GSH reached 669.3 mg/L, which was increased by 124.6% compared to that without amino acid addition.