A single Sfp-type phosphopantetheinyl transferase plays a major role in the biosynthesis of PKS and NRPS derived metabolites in Streptomyces ambofaciens ATCC23877.
The phosphopantetheinyl transferases (PPTases) are responsible for the activation of the carrier protein domains of the polyketide synthases (PKS), non ribosomal peptide synthases (NRPS) and fatty acid synthases (FAS). The analysis of the Streptomyces ambofaciens ATCC23877 genome has revealed the presence of four putative PPTase encoding genes. One of these genes appears to be essential and is likely involved in fatty acid biosynthesis. Two other PPTase genes, samT0172 (alpN) and samL0372, are located within a type II PKS gene cluster responsible for the kinamycin production and an hybrid NRPS-PKS cluster involved in antimycin production, respectively, and their products were shown to be specifically involved in the biosynthesis of these secondary metabolites. Surprisingly, the fourth PPTase gene, which is not located within a secondary metabolite gene cluster, appears to play a pleiotropic role. Its product is likely involved in the activation of the acyl- and peptidyl-carrier protein domains within all the other PKS and NRPS complexes encoded by S. ambofaciens. Indeed, the deletion of this gene affects the production of the spiramycin and stambomycin macrolide antibiotics and of the grey spore pigment, all three being PKS-derived metabolites, as well as the production of the nonribosomally produced compounds, the hydroxamate siderophore coelichelin and the pyrrolamide antibiotic congocidine. In addition, this PPTase seems to act in concert with the product of samL0372 to activate the ACP and/or PCP domains of the antimycin biosynthesis cluster which is also responsible for the production of volatile lactones.
Université de Lorraine, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France ; INRA, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France.
Robert
R
Bunet
Institute of Organic Chemistry, TU Braunschweig, Braunschweig, Germany.
Ramona
R
Riclea
Université de Lorraine, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France ; INRA, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France.
Luisa
L
Laureti
Université de Lorraine, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France ; INRA, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France.
Laurence
L
Hôtel
Université de Lorraine, Laboratoire d'Ingénierie des Biomolécules, Ecole Nationale Supérieure d'Agronomie et des Industries Alimentaires, Vandœuvre-lès-Nancy, France.
Cédric
C
Paris
Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux (URAFPA), Vandœuvre-lès-Nancy Cedex, France ; INRA,URAFPA, USC 340, Vandœuvre-lès-Nancy, France.
Jean-Michel
JM
Girardet
Department of Biology, Chemical Ecology/Biological Chemistry, University of Konstanz, Konstanz, Germany.
Dieter
D
Spiteller
Institute of Organic Chemistry, TU Braunschweig, Braunschweig, Germany.
Jeroen S
JS
Dickschat
Université de Lorraine, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France ; INRA, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France.
Pierre
P
Leblond
Université de Lorraine, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France ; INRA, Dynamique des Génomes et Adaptation Microbienne, UMR 1128, Vandœuvre-lès-Nancy, France.
Bertrand
B
Aigle
D000968:Antimycin A / Q000031:analogs & derivatives / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D009429:Netropsin / Q000378:metabolism; D009842:Oligopeptides / Q000096:biosynthesis / Q000235:genetics; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D009842:Oligopeptides; C412862:coelichelin; C082662:phosphopantetheinyl transferase; C032456:antimycin; D000968:Antimycin A; D009429:Netropsin; D048630:Polyketide Synthases; D017855:Transferases (Other Substituted Phosphate Groups); D010453:Peptide Synthases