Biosynthetic Origin of the Antibiotic Pseudopyronines A and B in Pseudomonas putida BW11M1. Issue 17 (28th October 2015)

• Record Type: Journal Article
• Authors: Bauer, Judith S.; Ghequire, Maarten G. K.; Nett, Markus; Josten, Michaele; Sahl, Hans‐Georg; De Mot, René; Gross, Harald
• Is Part Of: Chembiochem. Volume 16:Issue 17(2015)
• Page Start: 2491
• Page End: 2497
• Publication Date: 2015-10-28
• Subjects: alpha-pyrone -- biosynthesis -- natural products -- PpyS -- Pseudomonas -- sch 419560; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500413
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Within the framework of our effort to discover new antibiotics from pseudomonads, pseudopyronines A and B were isolated from the plant‐derived Pseudomonas putida BW11M1. Pseudopyronines are 3, 6‐dialkyl‐4‐hydroxy‐2‐pyrones and displayed high in vitro activities against several human pathogens, and in our hands also towards the plant pathogen Pseudomonas savastanoi . Here, the biosynthesis of pseudopyronine B was studied by a combination of feeding experiments with isotopically labeled precursors, genomic sequence analysis, and gene deletion experiments. The studies resulted in the deduction of all acetate units and revealed that the biosynthesis of these α‐pyrones occurs with a single PpyS‐homologous ketosynthase. It fuses, with some substrate flexibility, a 3‐oxo‐fatty acid and a further unbranched saturated fatty acid, both of medium chain‐length and provided by primary metabolism. Abstract : Only one enzyme does the job . Dialkylpyrones are commonly biosynthesized by polyketidic systems. However, in the case of the dialkylpyrones pseudopyronines A and B, mutagenic experiments correlated their biosynthesis to a single ppyS ‐like gene. Isotopic labelling experiments support a two‐chain mechanism in which two fatty acids are fused by PpyS to give the secondary metabolite pseudopyronine.