Enhancing Substrate Preference of Iridoid Synthase via Focused Polarity-Steric Mutagenesis Scanning.

ABSTRACT: Nepetalactol serves as the scaffold for most iridoids, which exhibit a wide range of biological and pharmacological activities. Iridoid synthase (ISY) plays a crucial role in the in vivo synthesis of nepetalactol from 8-oxogeranial. However, the substrate promiscuity of ISY could result in a deviation of flux toward off-target routes. In this work, the substrate preference (SP, the ratio of activity for 8-oxogeranial to geranial) of ISY for nepetalactol was improved by directed evolution. First, the strategy of focused polarity-steric mutagenesis scanning (FPSMS) was performed to construct a small mutant library with NmISY2 from Nepeta mussinii as an object. Four amino acid residues with varying polarity and steric hindrance, including alanine, aspartic acid, serine, a

SUBMITTER: Yu H 

PROVIDER: S-EPMC11835258 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature