Microbial engineering for the production of chemical and pharmaceutical products from the isoprenoid pathway

A method for making a pharmaceutical product, the method comprising:

• providing an Escherichia coli (E. coli) that produces isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) through an upstream methylerythritol pathway (MEP) and converts the IPP and DMAPP to squalene or derivative thereof through a recombinantly expressed downstream synthesis pathway comprising farnesyl diphosphate synthase and squalene synthase;
• culturing the E. coli to produce the squalene or derivative thereof, wherein the accumulation of indole in the culture is controlled to below 100 mg/L to thereby increase production of squalene or derivative thereof;
• and
• incorporating the squalene or derivative thereof, into a pharmaceutical product.

A method for making a terpenoid, the method comprising:

• providing an Escherichia coli (E. coli) that produces isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) through an upstream methylerythritol pathway (MEP) and converts the IPP and DMAPP to squalene or derivative thereof through a recombinantly expressed downstream synthesis pathway comprising farnesyl diphosphate synthase and squalene synthase;
• and
• culturing the E. coli to produce the squalene or derivative thereof, wherein the accumulation of indole in the culture is controlled to below 100 mg/L to thereby increase terpenoid production;
• and recovering the squalene or derivative thereof.