Enhanced S-Adenosylmethionine Production by Increasing ATP Levels in Baker's Yeast (Saccharomyces cerevisiae)

In the biosynthesis of S-adenosylmethionine (SAM) in baker's yeast (Saccharomyces cerevisiae), ATP functions as both a precursor and a driving force. However, few published reports have dealt with the control of ATP concentration using genetic design. In this study we have adopted a new ATP regulation strategy in yeast for enhancing SAM biosynthesis, including altering NADH availability and regulating the oxygen supply. Different ATP regulation systems were designed based on the introduction of water-forming NADH oxidase, Vitreoscilla hemoglobin, and phosphite dehydrogenase in combination with overexpression of the gene SAM2. Via application of this strategy, after 28 h cultivation, the SAM titer in the yeast strain ABYSM-2 reached a maximum level close to SS mg/L, an increase of 67% compared to the control strain. The results show that the ATP regulation strategy is a valuable tool for SAM production and might further enhance the synthesis of other ATP-driven metabolites in yeast.