초록
<P><B>Abstract</B></P> <P>The aim of this work was to enhance mevalonate yield from glucose in <I>Escherichia coli</I> 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 <I>E. coli</I> introducing <I>mvaE</I> and <I>mvaS</I> genes from <I>Enterococcus faecalis</I>. Sulfur starvation resulted in the highest mevalonate yield of 0.61C-molC-mol<SUP>−1</SUP> from glucose. The metabolic impacts of nutrient starvation were investigated by <SUP>13</SUP>C-metabolic flux analysis. Under nitrogen starvation, the flux of the TCA cycle was large, causing high CO<SUB>2</SUB> 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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sulfur starvation achieved highest mevalonate yield of 0.61C-mol/C-mol in <I>E. coli</I>. </LI> <LI> Degradation of MvaE enzyme caused a large TCA cycle flux under nitrogen starvation. </LI> <LI> TCA cycle flux was suppressed under magnesium or sulfur starvation. </LI> <LI> Mevalonate synthesis was reduced by NADPH supply shortage under magnesium starvation. </LI> <LI> Low TCA cycle flux and enough NADPH production led high yield in sulfur starvation. </LI> </UL> </P>