Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids

Recombinant bacterial or yeast cells capable of increased production of mevalonate, wherein the cells comprise an attenuated activity of phosphogluconolactonase (PGL), wherein the recombinant bacterial or yeast cells further comprise (i) and (ii):

• (i) modulated activity of two or more enzymes from the group consisting of:
• (a) decreased activity of citrate synthase,
• (b) attenuated activity of phosphotransacetylase,
• (c) attenuated activity of acetate kinase,
• (d) attenuated activity of lactate dehydrogenase,
• (e) increased activity of malate dehydrogenase,
• (f) increased activity of pyruvate dehydrogenase,
• (g) attenuated activity of phosphoenolpyruvate carboxylase, resulting in increased carbon flux towards mevalonate production;
• and
• (ii) one or more nucleic acids encoding one or more upper mevalonate (MVA) pathway polypeptides;
• and wherein the cells produce increased amounts of mevalonate compared to mevalonate-producing cells that do not comprise (i) and (ii).