An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens.
Congocidine (netropsin) is a pyrrole-amide (oligopyrrole, oligopeptide) antibiotic produced by Streptomyces ambofaciens. We have identified, in the right terminal region of the S. ambofaciens chromosome, the gene cluster that directs congocidine biosynthesis. Heterologous expression of the cluster and in-frame deletions of 8 of the 22 genes confirm the involvement of this cluster in congocidine biosynthesis. Nine genes can be assigned specific functions in regulation, resistance, or congocidine assembly. In contrast, the biosynthetic origin of the precursors cannot be easily inferred from in silico analyses. Congocidine is assembled by a nonribosomal peptide synthetase (NRPS) constituted of a free-standing module and several single-domain proteins encoded by four genes. The iterative use of its unique adenylation domain, the utilization of guanidinoacetyl-CoA as a substrate by a condensation domain, and the control of 4-aminopyrrole-2-carboxylate polymerization constitute the most original features of this NRPS.
Juguet
Maud
M
Institut de Génétique et Microbiologie, University Paris Sud 11, CNRS, UMR 8621, 91405 Orsay, France.
Lautru
Sylvie
S
Francou
François-Xavier
FX
Nezbedová
Sárka
S
Leblond
Pierre
P
Gondry
Muriel
M
Pernodet
Jean-Luc
JL
D000105:Acetyl Coenzyme A / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005810:Multigene Family; D009429:Netropsin / Q000096:biosynthesis*; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000201:enzymology*
D001426:Bacterial Proteins; D009429:Netropsin; D000105:Acetyl Coenzyme A; D010453:Peptide Synthases