Work

Sequence-function space of radical SAM cyclophane synthases reveal conserved active site residues that influence substrate specificity

Year: 2024

Type: article

Abstract: Phan C.-S., Morinaka B. I. Sequence-function space of radical SAM cyclophane synthases reveal conserved active site residues that influence substrate specificity. RSC Chem. Biol. 2024, 5, 1195-1200. Abstract: Radical SAM cyclophane synthases catalyze C–C, C–N, and C–O crosslinking reactions in the biosynthesis of bioactive peptide natural products. Here, we studied an uncharacterized rSAM enzyme, HtkB from Pandoraea sp., and found this enzyme to catalyze the formation of a HisC2-to-LysCβ crosslink. We used a combination of ColabFold and mutagenesis studies to show that residues D214 in HtkB and H204 in HaaB (another cyclophane synthase) are important for substrate specificity. Mutation of these residues changes the specificity and lowers substrate recognition on the wild-type motifs. This result opens opportunities to alter the specificity and promiscuity for rSAM peptide modifying enzymes.

Source: Zenodo (CERN European Organization for Nuclear Research)

DOI: 10.5281/zenodo.17249821

Authors: Phan, Chin-Soon, Morinaka, Brandon I.

Institution: National University of Singapore

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: European Commission

Award: Natural Products Research at Latvian Institute of Organic Synthesis as a driver for Excellence in Innovation