Structure and Function of a Dual Reductase–Dehydratase Enzyme System Involved in p-Terphenyl Biosynthesis
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.
Clinger, J. A.; Zhang, Y.; Liu, Y.; Miller, M. D.; Hall, R. E.; Van Lanen, S. G.; Phillips Jr., G. N.; Thorson, J. S.; Elshahawi, S. I. Structure and Function of a Dual Reductase–Dehydratase Enzyme System Involved in p -Terphenyl Biosynthesis. ACS Chem. Biol. 2021, 16 (12), 2816–2824.https://doi.org/10.1021/acschembio.1c00701
American Chemical Society