title: Biosynthetic origin of the antibiotic cyclocarbamate brabantamide A (SB-253514) in plant-associated Pseudomonas.
abstract: 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.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schmidt
authors.forename: Menno
authors.initials: M
authors.lastname: van der Voort
authors.forename: Max
authors.initials: M
authors.lastname: Crüsemann
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
authors.forename: Michaele
authors.initials: M
authors.lastname: Josten
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Henrike
authors.initials: H
authors.lastname: Miess
authors.forename: Jos M
authors.initials: JM
authors.lastname: Raaijmakers
authors.forename: Harald
authors.initials: H
authors.lastname: Gross
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D020868:Gene Silencing; D005810:Multigene Family; D010944:Plants / Q000382:microbiology*; D017434:Protein Structure, Tertiary; D011549:Pseudomonas / Q000235:genetics / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011714:Pyrans; C414127:SB 253514; D000249:Adenosine Monophosphate