Abstract
The aim of this work was to enhance mevalonate yield from glucose in Escherichia coli by essential nutrient starvations and to reveal these effects on the central carbon metabolism. Stationary phase culture without essential nutrients such as nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation resulted in the highest mevalonate yield of 0.61C-molC-mol−1 from glucose. The metabolic impacts of nutrient starvation were investigated by 13C-metabolic flux analysis. Under nitrogen starvation, the flux of the TCA cycle was large, causing high CO2 production. This was caused by degradation of mevalonate synthesis pathway enzymes. Under magnesium starvation, NADPH production was decreased, which limited mevalonate synthesis and promoted an overflow of acetate. Sulfur starvation not only suppressed the TCA cycle flux, but also supplied NADPH for mevalonate synthesis.
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