Key elements and regulation strategies of NRPSs for biosynthesis of lipopeptides by Bacillus

Lipopeptides are a group of second metabolites of Bacillus and have multiple activities such as inhibiting fungi, bacteria, viruses, and tumors, showing a great potential application in agricultural and biomedical fields. However, low production severely restrained their application in practice. Deeply understanding the key elements of lipopeptide synthesis and the regulatory strategies is essential to target the improvement of lipopeptide production. The synthetic pathways of different lipopeptides are different, but closely and mutually interfered. The loading of fatty acid chains and the extension of peptide chains are two key steps for the synthesis of different lipopeptides by Bacillus. The selection of fatty acid chains, the loading order of amino acids, and the recognition of the final cyclization site are the critical steps to determine the end products of different lipopeptides. In order to find the key elements for precisely directing the formation of different lipopeptides by Bacillus, the key structural elements and possible regulatory strategies that have been reported in the production of different lipopeptides, mainly surfactin, iturin, and fengycin by Bacillus, were summarized and compared. The possible ways to improve the production of different targeted lipopeptides were proposed. KEY POINTS: • The selectivity of fatty acids is determined by specific domains. • The COM domain and the PKS docking domain determine the order of amino acids. • The regulation patterns of different domains for lipopeptide synthesis are different. • The regulation of different lipopeptide products overlaps each other.