Multifunctional polyketide-peptide synthetase essential for albicidin biosynthesis in Xanthomonas albilineans

Albicidins, a family of potent antibiotics and phytotoxins produced by the sugarcane leaf scald pathogen Xanthomonas albilineans, inhibit DNA replicat ion in bacteria and plastids. A gene located by Tn5-tagging was confirmed b y complementation to participate in albicidin biosynthesis. The gene (xabB) encodes a large protein (predicted M, 525 695), with a modular architectur e indicative of a multifunctional polyketide synthase (PKS) linked to a non -ribosomal peptide synthetase (NRPS). At 4801 amino acids in length, XabB i s the largest reported PKS-NRPS. Twelve catalytic domains in this multifunc tional enzyme are arranged in the order N terminus-acyl-CoA ligase (AL)-acy l carrier protein (ACP)-beta -ketoacyl synthase (KS)-beta -ketoacyl reducta se (KR)-ACP-ACP-KS-peptidyl carrier protein (PCP)-condensation (C)-adenylat ion-PCP-C. The modular architecture of XabB indicates likely steps in albic idin biosynthesis and approaches to enhance antibiotic yield. The novel pat tern of domains, in comparison with known PKS-NRPS enzymes for antibiotic p roduction, also contributes to the knowledge base for rational design of en zymes producing novel antibiotics.