McHugh, R. E., Munnoch, J. T., Braes, R. E., McKean, I. J. W., Giard, J., Taladriz-Sender, A., Peschke, F., Burley, G. A., Roe, A. J. and Hoskisson, P. A. (2022) Biosynthesis of aurodox, a type III secretion system inhibitor from streptomyces goldiniensis. Applied and Environmental Microbiology, 88(15), e0069222. (doi: 10.1128/aem.00692-22) (PMID:35867559) (PMCID:PMC9361827)
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Abstract
The global increase in antimicrobial-resistant infections means that there is a need to develop new antimicrobial molecules and strategies to combat the issue. Aurodox is a linear polyketide natural product that is produced by Streptomyces goldiniensis, yet little is known about aurodox biosynthesis or the nature of the biosynthetic gene cluster (BGC) that encodes its production. To gain a deeper understanding of aurodox biosynthesis by S. goldiniensis, the whole genome of the organism was sequenced, revealing the presence of an 87 kb hybrid polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) BGC. The aurodox BGC shares significant homology with the kirromycin BGC from S. collinus Tϋ 365. However, the genetic organization of the BGC differs significantly. The candidate aurodox gene cluster was cloned and expressed in a heterologous host to demonstrate that it was responsible for aurodox biosynthesis and disruption of the primary PKS gene (aurAI) abolished aurodox production. These data supported a model whereby the initial core biosynthetic reactions involved in aurodox biosynthesis followed that of kirromycin. Cloning aurM* from S. goldiniensis and expressing this in the kirromycin producer S. collinus Tϋ 365 enabled methylation of the pyridone group, suggesting this is the last step in biosynthesis. This methylation step is also sufficient to confer the unique type III secretion system inhibitory properties to aurodox.
| Item Type: | Articles |
|---|---|
| Additional Information: | We thank the University of Strathclyde and the University of Glasgow for jointly funding the Ph.D. of REM. A.J.R., and P.A.H. would like to acknowledge funding from Medical Research Council (MRC) (MR/V011499/1). P.A.H. would also like to acknowledge funding from Biotechnology and Biological Sciences Research Council (BBSRC) (BB/ T001038/1 and BB/T004126/1) and the Royal Academy of Engineering Research Chair Scheme for long-term personal research support (RCSRF2021\11\15). |
| Keywords: | Ecology, Applied Microbiology and Biotechnology, Food Science, Biotechnology |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Roe, Professor Andrew and McHugh, Ms Rebecca |
| Authors: | McHugh, R. E., Munnoch, J. T., Braes, R. E., McKean, I. J. W., Giard, J., Taladriz-Sender, A., Peschke, F., Burley, G. A., Roe, A. J., and Hoskisson, P. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Applied and Environmental Microbiology |
| Publisher: | American Society for Microbiology. |
| ISSN: | 0099-2240 |
| ISSN (Online): | 1098-5336 |
| Published Online: | 18 July 2022 |
| Copyright Holders: | Copyright © 2022 McHugh et al. |
| First Published: | First published in Applied and Environmental Microbiology 88(15): e0069222 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Data DOI: | 10.6084/m9.figshare.19140005.v1 |
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