Structure and Function of a Dual Reductase–Dehydratase Enzyme System Involved in p-Terphenyl Biosynthesis

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We report the identification of the ter gene cluster responsible for the formation of the p-terphenyl derivatives terfestatins B and C and echoside B from the Appalachian Streptomyces strain RM-5–8. We characterize the function of TerB/C, catalysts that work together as a dual enzyme system in the biosynthesis of natural terphenyls. TerB acts as a reductase and TerC as a dehydratase to enable the conversion of polyporic acid to a terphenyl triol intermediate. X-ray crystallography of the apo and substrate-bound forms for both enzymes provides additional mechanistic insights. Validation of the TerC structural model via mutagenesis highlights a critical role of arginine 143 and aspartate 173 in catalysis. Cumulatively, this work highlights a set of enzymes acting in harmony to control and direct reactive intermediates and advances fundamental understanding of the previously unresolved early steps in terphenyl biosynthesis.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in ACS Chemical Biology, volume 16, issue 12, in 2021 following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at


American Chemical Society