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

Figure 1

Relationships among the polymyxin E biosynthesis-related genes [13–17, 27]. Polymyxin E is biosynthesized by a multienzyme system named NRPS, which is comprised of three synthetases PmxA, PmxB, and PmxE encoded by pmxA, pmxB, and pmxE, respectively. PmxA comprises four modules whose amino acid substrates are D-Leu, L-Leu, L-Dab, and L-Dab. PmxB composes only one module with L-Thr as its amino acid substrate. PmxE has five modules whose amino acid substrates are L-Dab, L-Thr, L-Dab, L-Dab, and L-Dab. Based on the polymyxin E structure, the order of modules for amino acid assembly during polymyxin E synthesis is PmxE-PmxA-PmxB, which is consistent with the order of ten amino acid groups on polymyxin E molecule. The multienzyme system is probed and activated by phosphopantetheinyl transferase (Sfp) encoded by sfp. The pmxA expression is negatively regulated by a DNA-binding protein, AbrB encoded by abrB. The abrB expression is negatively regulated by another DNA-binding protein, Spo0A encoded by spo0A. Polymyxin E is secreted by ABC transporters PmxC and PmxD encoded by pmxC and pmxD, respectively. Dab is synthesized from L-asp-semialdehyde (L-Asp) by EctB which is encoded by ectB. Fatty acid: 6-methyloctanoic acid or isooctanoic acid; Thr: threonine; Phe: phenylalanine; Leu: leucine; and Dab: α,γ-diaminobutyric acid.