Metabolic engineering for microbial production of terpenoid products

A method for production of a terpene or terpenoid, comprising:

• providing a bacterial strain that produces isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through an upstream methylerythritol pathway (MEP) and converts the IPP and DMAPP to a terpene or terpenoid through a downstream synthesis pathway;
• and
• culturing the bacterial strain in culture media to produce the terpene or terpenoid, wherein greater than 15% of carbon entering glycolysis becomes MEP carbon;
• wherein the bacterial strain overexpresses 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr) and 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE), such that expression levels of Dxr and IspE in the bacterial strain limits accumulation of each of 1-deoxy-D-xylulose (DOX) and 2-C-methyl-D-erythritol (ME) in the culture media to 1 g/L or less;
• wherein the bacterial strain further overexpresses 1-hydroxy-2-methyl-2-E-butenyl 4-diphosphate synthase (IspG) and 1-hydroxy-2-methyl-2-(E) 4-diphosphate reductase (IspH), such that expression levels of IspG and IspH in the bacterial cell limits accumulation of 2C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) in the culture media.