POLYMYXIN SYNTHETASE AND GENE CLUSTER THEREOF

摘要

A polymyxin synthetase and a gene cluster thereof are provided to increase productivity of polymyxin, and develop polymyxin having minimized side effects and new antibiotics based on polymyxin. The gene cluster encodes at least one polypeptide associated with synthesis of polymyxin selected from Pmx A, Pmx B, Pmx E and mutants thereof, and is isolated from Paenibacillus polymyxa E681, wherein the polymyxin is polymyxin B, polymyxin E or polymyxin M; and the genes encoding Pmx A, Pmx B and Pmx E have the nucleotide sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, respectively. The polymyxin synthetase comprises Pmx A, Pmx B and Pmx E polypeptides having the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, wherein each of polypeptides contains one or more modules and each of modules contains two or more domains selected from A, C, T, E and TE domains. A method for producing the polymyxin comprises the steps of: (1) preparing a recombinant vector containing the gene cluster encoding the polymyxin synthetase; (2) transforming a host cell with the recombinant vector; (3) culturing the transformed host cell; and (4) isolating and purifying the polymyxin from the cultured medium.