The intensive use of chemical pesticides to treat plant diseases has resulted in various problems such as severe environmental pollution, food safety concerns, and emergence of drug resistance. Biological control using microorganisms or their metabolites, a more rational and safer method, has emerged as a promising alternative to suppress plant pathogens and reduce the use of agrochemicals [1
]. Pelgipeptins, a group of natural active compounds isolated from Paenibacillus elgii
B69, are potential biological control agents [1
]. This group of antibiotics has a general structure composed of a cyclic nonapeptide moiety and a β-hydroxy fatty acid. Four analogues of pelgipeptin have been identified and characterised [3
]. These analogues are highly similar in structure and differ only in one amino acid unit or in the lipid acid (FigureA). Pelgipeptin exhibits broad-spectrum antimicrobial activity against pathogenic bacteria and fungi, including Staphylococcus aureusEnterococcus faecalisEscherichia coliCandida albicansFusarium oxysporumF. graminearumF. moniliformeRhizoctonia solani
, and Colletotrichum lini
]. This compound effectively inhibited the development of sheath blight caused by R. solani
on rice in a preliminary evaluation of the in vivo
efficacy of pelgipeptin [1
Pelgipeptin and the genes responsible for its biosynthesis. (A) Primary structure of pelgipeptin. (B) The plp gene cluster and domain organisation of the NRPS.
Similar to polymyxin and fusaricidin from P. polymyxa,
pelgipeptin, containing non-proteinogenic and D-amino acids, must be synthesised by a non-ribosomal peptide synthetase (NRPS). NRPS is a large multifunctional enzyme that has modular structures [4
]. Each NRPS module catalyses the incorporation of a specific substrate into the growing product. A typical module consists of three enzymatic domains, namely, adenylation (A), thiolation (T; also known as peptidyl carrier protein), and condensation (C) domains. The A domain selects and activates a specific amino acid substrate, the T domain is responsible for tethering the activated substrate to the 4′-phosphopanthetheinyl cofactor, and the C domain catalyses peptide bond formation between the elongating peptide and a new amino acid. In addition to these core domains, the terminal thioesterase (TE) and epimerisation (E) domains, as well as several other tailoring domains, may also be present in NRPS modules. The order of modules of an NRPS is, in many cases, collinear to the amino acid sequence of the corresponding peptide product. The collinearity rule of NRPS systems combined with knowledge of the specificity-conferring code of A domain allow for the prediction and amino acid modification of peptide fragments synthesised by corresponding NRPS [5
]. However, few NRPS sequences have been extensively described in comparison with the number of known peptide products, limiting the study of the principles of non-ribosomal peptide synthesis and the development of new bioactive peptides by genetic engineering. In this study, we identified and analysed a gene cluster involved in the biosynthesis of pelgipeptin and provided biochemical data for the collinearity of this peptide assembly line.