Scheme 1 - Pathway for in vivo production of 8-hydroxycadinene and artemisinic acid in E. coli.

Biosynthesis of terpenoids takes place through a common pathway involving the condensation of the C₅ building blocks isopentenyl diphosphate (IPP, Compound 13) and dimethylallyl diphosphate (DMAPP, Compound 14), which can be condensed by prenyltransferases to yield linear diphosphate intermediates of varying sizes, such as FPP (Compound 15). Cyclization, coupling, and/or rearrangement catalyzed by terpene synthases produces the diverse carbon backbones observed in terpene natural products. The parental carbon skeletons are then extensively tailored by multiple transformations including oxidation, reduction, isomerization, hydration, and conjugation to yield structurally complex and diverse natural products such as gossypol (Compound 1) and artemisinin (Compound 2). AtoB, acetyl-CoA acetyltransferase; HMGS, hydroxymethylglutaryl-CoA synthase (ERG13); tHMGR, truncated hydroxymethylglutaryl-CoA reductase (HMG1); MK, mevalonate kinase (ERG12); PMK, phosphomevalonate kinase (ERG8); PMD, phosphomevalonate decarboxylase (ERG19); IDI, isopentenyl diphosphate-isomerase; IspA, farnesyl diphosphate synthase; CAS, cadinene synthase; CAH, cadinene hydroxylase; CPR, P450 reductase; ADS, amorphadiene synthase; AMO, amorphadiene oxidase.