Tools
Tools
Moffat, Alaster D., Höing, Lars, Santos-Aberturas, Javier, Markwalder, Tim, Malone, Jacob G. 
ORCID: https://orcid.org/0000-0003-1959-6820, Teufel, Robin and Truman, Andrew W.
(2024)
Understanding the biosynthesis, metabolic regulation, and anti-phytopathogen activity of 3,7-dihydroxytropolone in Pseudomonas spp.
mBIO, 15 (10).
ISSN 2150-7511
Preview |
PDF (moffat-et-al-2024-understanding-the-biosynthesis-metabolic-regulation-and-anti-phytopathogen-activity-of-3-7)
- Published Version
Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
The genus Pseudomonas is a prolific source of specialized metabolites with significant biological activities, including siderophores, antibiotics, and plant hormones. These molecules play pivotal roles in environmental interactions, influencing pathogenicity, inhibiting microorganisms, responding to nutrient limitation and abiotic challenges, and regulating plant growth. These properties mean that pseudomonads are suitable candidates as biological control agents against plant pathogens. Multiple transposon-based screens have identified a Pseudomonas biosynthetic gene cluster (BGC) associated with potent antibacterial and antifungal activities, which produces 7-hydroxytropolone (7-HT). In this study, we show that this BGC also makes 3,7-dihydroxytropolone (3,7-dHT), which has strong antimicrobial activity toward Streptomyces scabies, a potato pathogen. Through metabolomics and reporter assays, we unveil the involvement of cluster-situated genes in generating phenylacetyl-coenzyme A, a key precursor for tropolone biosynthesis via the phenylacetic acid catabolon. The clustering of these phenylacetic acid genes within tropolone BGCs is unusual in other Gram-negative bacteria. Our findings support the interception of phenylacetic acid catabolism via an enoyl-CoA dehydratase encoded in the BGC, as well as highlighting an essential role for a conserved thioesterase in biosynthesis. Biochemical assays were used to show that this thioesterase functions after a dehydrogenation–epoxidation step catalyzed by a flavoprotein. We use this information to identify diverse uncharacterized BGCs that encode proteins with homology to flavoproteins and thioesterases involved in tropolone biosynthesis. This study provides insights into tropolone biosynthesis in Pseudomonas, laying the foundation for further investigations into the ecological role of tropolone production.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | pseudomonas,biosynthesis,biosynthetic gene cluster,natural antimicrobial products,specialized metabolism,microbiology,virology ,/dk/atira/pure/subjectarea/asjc/2400/2404 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 04 Nov 2024 12:30 |
| Last Modified: | 12 Nov 2024 14:31 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97454 |
| DOI: | 10.1128/mbio.01022-24 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |