Sodium formate redirects carbon flux and enhances heterologous mevalonate production in Methylobacterium extorquens AM1

Methylobacterium extorquens AM1 (AM1), a model strain of methylotrophic cell factories (MeCFs) could be used to produce fine chemicals from methanol. Synthesis of heterologous products usually needs reducing cofactors, but AM1 growing on methanol lack reducing power. Formate could be used as a reducing agent. In this study, mevalonic acid (MEV) yield of 0.067 gMEV/g methanol was reached by adding 10 mmol L-1 sodium formate in MEV accumulating stage (at 72 h). The yield was improved by 64.57%, and represented the highest yield reported to date. 13 C-labeling experiments revealed global effects of sodium formate on metabolic pathways in engineered Methylobacterium extorquens AM1. Sodium formate significantly increased the ratios of reducing equivalents, enhanced the metabolic rate of pathways demanding reducing cofactors and redirected the carbon flux to MEV synthesis. As a result, coupling formate to methanol-based production provide a promising way for converting C1 substances to useful chemical products.