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5.3 Artificial Cascade Reactions Involving P450s 121

Engineered
metabolic H H H
pathway
ADS CYP71AV1 CYP71AV1
Sugar FPP
H H H
HO HO
12 12
HO
Amorpha-4,11-diene Artemisinic alcohol
ADH1
Non-
H 2 O enzymatic
H Established H H
O chemistry CYP71AV1
O O ALDH1
H H H H
O HO H
12 12
H
O O O
Artemisinin Artemisinic acid Artemisinic aldehyde
Scheme 5.28 Cascade process in S. cerevisiae toward the artimisinin precursor artemisinic acid. Pathway engineering yields amorpha-
4,11-diene via farnesyl pyrophosphate (FPP), and oxidations of amorphadiene are catalyzed by CYP71AV1 (redox partner protein not
shown), alcohol dehydrogenase ADH1, and aldehyde dehydrogenase ALDH1. Artemisinin is synthesized in vitro from the produced
artemisinic acid by established synthetic chemistry. ADS, amorphadiene synthase.