title: Functional dissection of surfactin synthetase initiation module reveals insights into the mechanism of lipoinitiation.
abstract: Although the N-terminally attached fatty acids are key structural elements of nonribosomally assembled lipopeptide antibiotics, little is known about the mechanism of lipid transfer during the initial step of biosynthesis. In this study, we investigated the activity of the dissected initiation module (C-A(Glu)-PCP) of surfactin synthetase SrfAA in vitro to gain further insights into the lipoinitiation reaction. The dissected condensation (C) domain catalyzes the transfer of CoA-activated 3-hydroxy fatty acid with high substrate specificity at its donor site to the peptidyl carrier protein (PCP) bound amino acid glutamate (Glu(1)). Additionally, biochemical studies on four putative acyl CoA ligases in Bacillus subtilis revealed that two of them activate 3-hydroxy fatty acids for surfactin biosynthesis in vitro and that the disruption of corresponding genes has a significant influence on surfactin production.
authors.affiliation: Department of Chemistry, Biochemistry, Philipps-University Marburg, Hans-Meerwein-Strasse, D-35032 Marburg, Germany.
authors.forename: Femke I
authors.initials: FI
authors.lastname: Kraas
authors.forename: Verena
authors.initials: V
authors.lastname: Helmetag
authors.forename: Melanie
authors.initials: M
authors.lastname: Wittmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Strieker
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Marahiel
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D003066:Coenzyme A Ligases / Q000378:metabolism; D055666:Lipopeptides / Q000096:biosynthesis*; D009227:Myristic Acids / Q000378:metabolism; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D055666:Lipopeptides; D009227:Myristic Acids; C009893:beta-hydroxymyristic acid; D003066:Coenzyme A Ligases; D010453:Peptide Synthases; C069542:surfactin synthetase