A route to novel triterpenes

Abstract

Triterpenes are multiringed natural products useful as drugs, agrochemicals, and even cosmetics. Researchers report that a single amino acid mutation in the enzymes that synthesize these compounds can produce novel products with four-ring triterpene core structures instead of the usual five-ring ones (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1605509113). The modified enzymes could be engineered into microorganisms or plants to generate a variety of novel triterpenes that would be difficult or impossible to synthesize any other way. The researchers, led by Anne Osbourn of the John Innes Centre, notes that their findings reveal “hidden functional diversity within triterpene synthases.” They hope to use the mutant enzymes in a “triterpene machine” that yields custom-built triterpenes. Plants make triterpenes by using triterpene synthase enzymes to cyclize a linear substrate, 2,3-oxidosqualene, into pentacyclic natural products, such as the analgesic and anti-inflammatory agent β-amyrin. Other enzym...