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My favorite enzymes, parts 2 and 3

August 30, 2010

(Part 1: S-adenosylmethionine decarboxylase from T. brucei.)

I’ve previously noted the awesome catalytic power of orotidine monophosphate decarboxylase (OMPDC), so I will give it position #2 on my random-order list of favorite enzymes. The impressive rate enhancement of OMPDC has been of practical value to me during the past two years. When sharing the Plasmodium falciparum OMPDC with other labs, we haven’t had to send them very much because it’s so active.

Speaking of Plasmodium — the parasite that causes malaria — the best treatments for infection involve derivatives of artemisinin, a natural product of the plant Artemisia annua. Jay Keasling and his coworkers and collaborators have spent much of the past decade figuring out how to make artemisinin in high yields using yeast and bacteria as chemical factories. The full story is complicated, but a key discovery along the way was that A. annua contains a novel cytochrome P450 monooxygenase, CYP71AV1, which catalyzes three consecutive oxidation reactions at the C12 position of amorpha-4,11-diene, converting a methyl group (-CH3) to a carboxylic acid (-COOH). The final product is known as artemisinic acid.

Though a three-step oxidation by a P450 enzyme is not unprecedented, it is very convenient and very cool that cloning and characterization of a single enzyme brought Keasling et al. three steps closer to their goal of inexpensive, high-yield production of artemisinin. CYP71AV1 has thus earned spot #3 on my favorite-enzymes list.

[Reference: D.-K. Ro et al. (2006). Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440: 940-3. Figure 1 shows the oxidation steps mentioned above.]

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