Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas. Issue 2 (16th January 2014)

• Record Type: Journal Article
• Authors: Schmidt, Yvonne; van der Voort, Menno; Crüsemann, Max; Piel, Jörn; Josten, Michaele; Sahl, Hans‐Georg; Miess, Henrike; Raaijmakers, Jos M.; Gross, Harald
• Is Part Of: Chembiochem. Volume 15:Issue 2(2014)
• Page Start: 259
• Page End: 266
• Publication Date: 2014-01-16
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300527
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Within the framework of our genome‐based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A–C were isolated from plant‐associated <italic>Pseudomonas</italic> sp. SH‐C52. Brabantamides A–C displayed moderate to high in vitro activities against Gram‐positive bacterial pathogens. Their shared structure is unique in that they contain a 5, 5‐bicyclic carbamate scaffold. Here, the biosynthesis of brabantamide A (SB‐253514) was studied by a combination of bioinformatics, feeding experiments with isotopically labelled precursors and in vivo and in vitro functional analysis of enzymes encoded in the biosynthetic pathway. The studies resulted in the deduction of all biosynthetic building blocks of brabantamide A and revealed an unusual feature of this metabolite: its biosynthesis occurs via an initially formed linear di‐lipopeptide that is subsequently rearranged by a novel FAD‐dependent Baeyer–Villiger monooxygenase.</p> </abstract>