posted on 2021-11-12, 04:13authored byJonathan
A. Clinger, Yinan Zhang, Yang Liu, Mitchell D. Miller, Ronnie E. Hall, Steven G. Van Lanen, George N. Phillips Jr., Jon S. Thorson, Sherif I. Elshahawi
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.