TY - JOUR
T1 - Structure and Function of a Dual Reductase–Dehydratase Enzyme System Involved in p-Terphenyl Biosynthesis
AU - Clinger, Jonathan A.
AU - Zhang, Yinan
AU - Liu, Yang
AU - Miller, Mitchell D.
AU - Hall, Ronnie E.
AU - Van Lanen, Steven G.
AU - Phillips, George N.
AU - Thorson, Jon S.
AU - Elshahawi, Sherif I.
N1 - Publisher Copyright:
© 2021 American Chemical Society
PY - 2021/12/17
Y1 - 2021/12/17
N2 - 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.
AB - 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.
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U2 - 10.1021/acschembio.1c00701
DO - 10.1021/acschembio.1c00701
M3 - Article
C2 - 34763417
AN - SCOPUS:85119475206
SN - 1554-8929
VL - 16
SP - 2816
EP - 2824
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 12
ER -