Precursor Amino Acids Inhibit Polymyxin E Biosynthesis inPaenibacillus polymyxa, Probably by Affecting the Expression of Polymyxin E Biosynthesis-Associated Genes

Abstract

Polymyxin E belongs to cationic polypeptide antibiotic bearing four types of direct precursor amino acids including L-2,4-diaminobutyric acid (L-Dab), L-Leu, D-Leu, and L-Thr. The objective of this study is to evaluate the effect of addition of precursor amino acids during fermentation on polymyxin E biosynthesis inPaenibacillus polymyxa. The results showed that, after 35 h fermentation, addition of direct precursor amino acids to certain concentration significantly inhibited polymyxin E production and affected the expression of genes involved in its biosynthesis. L-Dab repressed the expression of polymyxin synthetase genespmxAandpmxE, as well as 2,4-diaminobutyrate aminotransferase geneectB; both L-Leu and D-Leu repressed thepmxAexpression. In addition, L-Thr affected the expression of not onlypmxA, but also regulatory genesspo0AandabrB. As L-Dab precursor, L-Asp repressed the expression ofectB,pmxA, andpmxE. Moreover, it affected the expression ofspo0AandabrB. In contrast, L-Phe, a nonprecursor amino acid, had no obvious effect on polymyxin E biosynthesis and those biosynthesis-related genes expression. Taken together, our data demonstrated that addition of precursor amino acids during fermentation will inhibit polymyxin E production probably by affecting the expression of its biosynthesis-related genes.