Work

Selective biosynthesis of a rhamnosyl nosiheptide by a novel bacterial rhamnosyltransferase

Year: 2024

Type: article

Abstract: Nosiheptide (NOS) is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. The hydroxyl group of 3-hydroxypyridine in NOS has been identified as a promising site for modification, which we therefore aimed to rhamnosylate. After screening, Streptomyces sp. 147326 was found to regioselectively attach a rhamnosyl unit to the 3-hydroxypyridine site in NOS, resulting in the formation of a derivative named NOS-R at a productivity of 24.6%. In comparison with NOS, NOS-R exhibited a 17.6-fold increase in aqueous solubility and a new protective effect against MRSA infection in mice, while maintaining a similar in vitro activity. Subsequently, SrGT822 was identified as the rhamnosyltransferase in Streptomyces sp. 147326 responsible for the biosynthesis of NOS-R using dTDP-L-rhamnose. SrGT822 demonstrated an optimal reaction pH of 10.0 and temperature of 55°C, which resulted in a NOS-R yield of 74.9%. Based on the catalytic properties and evolutionary analysis, SrGT822 is anticipated to be a potential rhamnosyltransferase for use in the modification of various complex scaffolds.

Source: Microbial Biotechnology

DOI: 10.1111/1751-7915.14412