RT Journal Article
SR Electronic
T1 Mechanistic basis for the emergence of EPS1 as a catalyst in plant salicylic acid biosynthesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.21.457228
DO 10.1101/2021.08.21.457228
A1 Michael P. Torrens-Spence
A1 Tianjie Li
A1 Ziqi Wang
A1 Christopher M. Glinkerman
A1 Jason O. Matos
A1 Yi Wang
A1 Jing-Ke Weng
YR 2021
UL http://biorxiv.org/content/early/2021/08/22/2021.08.21.457228.abstract
AB Unique to plants in the Brassicaceae family, the production of the plant defense hormone salicylic acid (SA) from isochorismate is accelerated by an evolutionarily young isochorismoyl-glutamate pyruvoyl-glutamate lyase, EPS1, which belongs to the BAHD acyltransferase protein family. Here, we report the crystal structures of apo and substrate-analog-bound EPS1 from Arabidopsis thaliana. Assisted by microsecond molecular dynamics simulations, we uncover a unique pericyclic rearrangement lyase mechanism facilitated by the active site of EPS1. We reconstitute the isochorismate-derived pathway of SA biosynthesis in Saccharomyces cerevisiae, which serves as an in vivo platform that helps identify active-site residues critical for EPS1 activity. This study describes the birth of a new catalyst in plant phytohormone biosynthesis by reconfiguring the ancestral active site of a progenitor enzyme to catalyze alternative reaction.One sentence summary By reconfiguring the active site of a progenitor acyltransferase-fold, EPS1 acquired the unique, evolutionarily new lyase activity that accelerates phytohormone salicylic acid production in Brassicaceae plants.Competing Interest StatementJ.K.W. is a member of the Scientific Advisory Board and a shareholder of DoubleRainbow Biosciences, Galixir and Inari Agriculture, which develop biotechnologies related to natural products, drug discovery and agriculture. All other authors have no competing interests.