title: Exploring the mechanism of lipid transfer during biosynthesis of the acidic lipopeptide antibiotic CDA.
abstract: The non-ribosomally synthesized lipodepsipeptide CDA belongs to the group of acidic lipopeptide antibiotics, whose members feature a fatty acid side chain that strongly affects their antimicrobial activity. This study elucidates the N-acylation of the N-terminal serine in the CDA peptide chain. This reaction is referred to as lipoinitiation and is shown to be catalyzed by the dissected starter C domain found at the N-terminus of Cda-PSI. The recombinantly produced C domain specifically interacts with 2,3-epoxyhexanoyl-S-ACP and catalyzes the transfer of the fatty acid moiety onto the amino group of PCP-bound serine with high selectivity for both carrier protein bound substrates at the donor and acceptor site.
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: Tobias W
authors.initials: TW
authors.lastname: Giessen
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Marahiel
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism; D000215:Acylation; D055162:Biocatalysis; D005227:Fatty Acids / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D048372:Streptomyces coelicolor / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; C040487:CDA antibiotic; D005227:Fatty Acids; D010455:Peptides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase