Utilization of high-K+-cane molasses for enhanced S-Adenosylmethionine production by manipulation of a K+ transport channel in Saccharomyces cerevisiae

Abstract

S-Adenosylmethionine (SAM) is a valuable compound extensively used in depression treatment and biological methyl donor, which is biosynthesized from ATP and L-methionine with SAM synthase (SAM-s) as a catalyst. In this research, the weak SAM-s activity was a key factor and led to low SAM titer in Saccharomyces cerevisiae. Then, a novel K+ uptake channel was introduced to the SAM production pathway of Saccharomyces cerevisiae, activated by K+ in molasses to enhance the SAM synthase (SAM-s) activity and thereby improve the production efficiency of SAM. As a result, the intracellular K+ concentration and SAM-s activity were 1.23- and 1.31-fold higher than the control leading to a 24 % increase to 0.93 ± 0.04 g/L in SAM titer. In combination with bioprocess optimization resulted in a final yield of 2.22 ± 0.01 g/L in shake flasks and 15.37 ± 0.89 g/L in a 5-L bioreactor from pretreated molasses. This work provides a practical and cost-effective strategy for the large-scale biosynthesis of SAM from cane molasses.