Differential Substrate Sensing in Terpene Synthases from Plants and Microorganisms: Insight from Structural, Bioinformatic, and EnzyDock Analyses

Renana Schwartz, Shani Zev, Dan T. Major

Research output: Contribution to journalArticlepeer-review

Abstract

Terpene synthases (TPSs) catalyze the first step in the formation of terpenoids, which comprise the largest class of natural products in nature. TPSs employ a family of universal natural substrates, composed of isoprenoid units bound to a diphosphate moiety. The intricate structures generated by TPSs are the result of substrate binding and folding in the active site, enzyme-controlled carbocation reaction cascades, and final reaction quenching. A key unaddressed question in class I TPSs is the asymmetric nature of the diphosphate-(Mg2+)3 cluster, which forms a critical part of the active site. In this asymmetric ion cluster, two diphosphate oxygen atoms protrude into the active site pocket. The substrate hydrocarbon tail, which is eventually molded into terpenes, can bind to either of these oxygen atoms, yet to which is unknown. Herein, we employ structural, bioinformatics, and EnzyDock docking tools to address this enigma. We bring initial data suggesting that this difference is rooted in evolutionary differences between TPSs. We hypothesize that this alteration in binding, and subsequent chemistry, is due to TPSs originating from plants or microorganisms. We further suggest that this difference can cast light on the frequent observation that the chiral products or intermediates of plant and bacterial terpene synthases represent opposite enantiomers.

Original languageEnglish
Article numbere202400743
JournalAngewandte Chemie - International Edition
Volume63
Issue number21
Early online date31 Mar 2024
DOIs
StatePublished - 21 May 2024

Keywords

  • Enzyme catalysis
  • microorganisms
  • plants
  • substrate binding
  • terpene synthases

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Catalysis

Fingerprint

Dive into the research topics of 'Differential Substrate Sensing in Terpene Synthases from Plants and Microorganisms: Insight from Structural, Bioinformatic, and EnzyDock Analyses'. Together they form a unique fingerprint.

Cite this