Browse by author
Lookup NU author(s): Professor Paul RaceORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). ChemBioChem published by Wiley-VCH GmbH. With growing understanding of complex biosynthetic pathways to natural products, mutasynthesis, which combines metabolic engineering with chemical synthesis, is becoming an increasingly important tool to produce novel compounds. Mupirocin, isolated from Pseudomonas fluorescens, is a mixture of pseudomonic acids (PAs) that exhibit antibiotic activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. We have developed a flexible approach, based on mutasynthesis, for the preparation of a library of novel PA analogues. The antimicrobial activities of the natural products and synthetic analogues were evaluated against Bacillus subtilis and four Staphylococcus aureus strains. Interestingly, one of the analogues retained antimicrobial activity in all the assays but lacked structural features that render PA-A unstable, that is, the 10,11-epoxide (replaced by an alkene) and ester linkage (replaced by a ketone). In addition, mutasynthesis allowed the preparation of an analogue of a key biosynthetic intermediate (desepoxy-PA-B) in which the C9 hydroxy fatty acid is replaced by a C7 analogue. Feeding studies with mutant strains of Pseudomonas fluorescens revealed that C7-desepoxy-PA-B was converted to the novel metabolite C7-PA-C with loss of the 8-hydroxyl group but with no extension to the C9 side chain.
Author(s): Husain SM, Wang L, Han L-C, Bowen JI, Song Z, de Courcy-Ireland F, Winter AJ, Simpson TJ, Race PR, Spencer J, Crump MP, Willis CL
Publication type: Article
Publication status: Published
Journal: ChemBioChem
Year: 2026
Volume: 27
Issue: 13
Print publication date: 14/07/2026
Online publication date: 30/06/2026
Acceptance date: 11/06/2026
Date deposited: 15/07/2026
ISSN (print): 1439-4227
ISSN (electronic): 1439-7633
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/cbic.70439
DOI: 10.1002/cbic.70439
Data Access Statement: The data that supports the findings of this study are available in the Supporting Information of this article.
Altmetrics provided by Altmetric
