Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB-253514) in Plant-Associated Pseudomonas

TY - JOUR

T1 - Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB-253514) in Plant-Associated Pseudomonas

AU - Schmidt, Y.

AU - van der Voort, M.

AU - Crüsemann, M.

AU - Piel, J.

AU - Josten, M.

AU - Sahl, H.-G.

AU - Miess, H.

AU - Raaijmakers, J.M.

AU - Gross, H.

N1 - Reporting year: 2014 Metis note: 5574; http://dx.doi.org/10.1002/cbic.201300527

PY - 2014

Y1 - 2014

N2 - 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. [KEYWORDS: biosynthesis carbamates monooxygenases peptides Pseudomonas SB-253514]

AB - 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. [KEYWORDS: biosynthesis carbamates monooxygenases peptides Pseudomonas SB-253514]

KW - international

U2 - 10.1002/cbic.201300527

DO - 10.1002/cbic.201300527

M3 - Article

SN - 1439-4227

VL - 15

SP - 259

EP - 266

JO - ChemBioChem

JF - ChemBioChem

IS - 2

ER -