A multifunctional polyketide-peptide synthetase essential for albicidin biosynthesis in Xanthomonas albilineans

Abstract

Albicidins, a family of potent antibiotics and phytotoxins produced by the sugarcane leaf scald pathogen Xanthomonas albilineans, inhibit DNA replication in bacteria and plastids. A gene located by Tn5-tagging was confirmed by complementation to participate in albicidin biosynthesis. The gene (xabB) encodes a large protein (predicted Mr 525695), with a modular architecture indicative of a multifunctional polyketide synthase (PKS) linked to a non-ribosomal peptide synthetase (NRPS). At 4801 amino acids in length, XabB is the largest reported PKS-NRPS. Twelve catalytic domains in this multifunctional enzyme are arranged in the order N terminus-acyl-CoA ligase (AL)-acyl carrier protein (ACP)-β-ketoacyl synthase (KS)-β-ketoacyl reductase (KR)-ACP-ACP-KS-peptidyl carrier protein (PCP)-condensation (C)-adenylation-PCP-C. The modular architecture of XabB indicates likely steps in albicidin biosynthesis and approaches to enhance antibiotic yield. The novel pattern of domains, in comparison with known PKS-NRPS enzymes for antibiotic production, also contributes to the knowledge base for rational design of enzymes producing novel antibiotics.