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Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas .
Author(s) -
Schmidt Yvonne,
van der Voort Menno,
Crüsemann Max,
Piel Jörn,
Josten Michaele,
Sahl HansGeorg,
Miess Henrike,
Raaijmakers Jos M.,
Gross Harald
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300527
Subject(s) - biosynthesis , pseudomonas , biochemistry , monooxygenase , biology , enzyme , metabolite , bacteria , stereochemistry , in vitro , chemistry , cytochrome p450 , genetics
Within the framework of our genome‐based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A–C were isolated from plant‐associated Pseudomonas 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.