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Lookup NU author(s): Professor Paul RaceORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or “stuttering” KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol).
Author(s): Winter AJ, Rowe MT, Weir ANM, Akter N, Mbatha SZ, Walker PD, Williams C, Song Z, Race PR, Willis CL, Crump MP
Publication type: Article
Publication status: Published
Journal: Angewandte Chemie - International Edition
Year: 2022
Volume: 61
Issue: 50
Print publication date: 12/12/2022
Online publication date: 13/10/2022
Acceptance date: 13/10/2022
Date deposited: 20/12/2023
ISSN (print): 1433-7851
ISSN (electronic): 1521-3773
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/anie.202212393
DOI: 10.1002/anie.202212393
PubMed id: 36227272
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