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

Jonathan A. Clinger, Yinan Zhang, Yang Liu, Mitchell D. Miller, Ronnie E. Hall, Steven G. Van Lanen, George N. Phillips, Jon S. Thorson, Sherif I. Elshahawi

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2816-2824
Number of pages9
JournalACS Chemical Biology
Volume16
Issue number12
DOIs
StatePublished - Dec 17 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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