PT  - JOURNAL ARTICLE
AU  - Michael P. Torrens-Spence
AU  - Tianjie Li
AU  - Ziqi Wang
AU  - Christopher M. Glinkerman
AU  - Jason O. Matos
AU  - Yi Wang
AU  - Jing-Ke Weng
TI  - Mechanistic basis for the emergence of EPS1 as a catalyst in plant salicylic acid biosynthesis
AID  - 10.1101/2021.08.21.457228
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.21.457228
4099  - http://biorxiv.org/content/early/2021/08/22/2021.08.21.457228.short
4100  - http://biorxiv.org/content/early/2021/08/22/2021.08.21.457228.full
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.