Volume 87 Issue 4 | p. 31 | Concentrates
Issue Date: January 26, 2009

Plant Enzyme Accepts Unnatural Substrates

Chemists at MIT have introduced an engineered biosynthetic enzyme that uses a wider range of substrates to forge alkaloid analogs
Department: Science & Technology

Chemists at MIT have introduced an engineered biosynthetic enzyme that accepts a wider range of substrates into periwinkle plant culture to make unnatural analogs of alkaloids (Nat. Chem. Biol., DOI: 10.1038/nchembio.141). The enzyme that Sarah E. O’Connor and Weerawat Runguphan inserted into the plant cells is the strictosidine synthase from the periwinkle's monoterpene indole alkaloid pathway. This pathway produces a variety of alkaloids, and the ability to make unnatural analogs could lead to compounds with new or improved medicinal properties. However, the pathway is complicated and poorly characterized, making production of these alkaloids in microbial systems a challenge, which is why the MIT scientists opted to reengineer the plant itself. Strictosidine synthase, which synthesizes strictosidine from secologanin and tryptamine, is a key bottleneck in the production of unnatural alkaloids because of its stringent substrate specificity. O’Connor and Runguphan transformed a mutant enzyme that accepts substituted tryptamine analogs into periwinkle cell culture. The substituted strictosidine produced by the enzyme is used in subsequent reactions in the pathway to produce unnatural alkaloid analogs such as substituted tabersonine.

Chemical & Engineering News
ISSN 0009-2347
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