Genome mining: Prediction of lipopeptides and polyketides from Bacillus and related Firmicutes

Abstract

Bacillus and related genera in the Bacillales within the Firmicutes harbor a variety of secondary metabolite gene clusters encoding polyketide synthases and non-ribosomal peptide synthetases responsible for remarkable diverse number of polyketides (PKs) and lipopeptides (LPs). These compounds may be utilized for medical and agricultural applications. Here, we summarize the knowledge on structural diversity and underlying gene clusters of LPs and PKs in the Bacillales. Moreover, we evaluate by using published prediction tools the potential metabolic capacity of these bacteria to produce type I PKs or LPs. The huge sequence repository of bacterial genomes and metagenomes provides the basis for such genome-mining to reveal the potential for novel structurally diverse secondary metabolites. The otherwise cumbersome task to isolate often unstable PKs and deduce their structure can be streamlined. Using web based prediction tools, we identified here several novel clusters of PKs and LPs from genomes deposited in the database. Our analysis suggests that a substantial fraction of predicted LPs and type I PKs are uncharacterized, and their functions remain to be studied. Known and predicted LPs and PKs occurred in the majority of the plant associated genera, predominantly in Bacillus and Paenibacillus. Surprisingly, many genera from other environments contain no or few of such compounds indicating the role of these secondary metabolites in plant-associated niches.

Identification and classification of known and putative antimicrobial compounds produced by a wide variety of Bacillales species

“…Among them, NRPs produced by Bacillales include lipopeptides (LPs) and others, with significant antimicrobial activity [136]. Here we present an extended collection based on members described in a previous review by Aleti et al [136]. By use of antiSMASH, we identified 31 types of putative NRPs, PKs and NRPS/PKS hybrid synthesized antimicrobials, which will be described in detail below.…”

“…are likely to be the main producers of LPs, which are mainly known for their antifungal properties [138–140]. Based on a previous genome mining work (see review Aleti et al [136]), we identified locillomycins as novel members of LPs in species of Bacillales (Additional file 3: Table S3).…”

“…Kurstakins form another family of LPs composed of four partially cyclic heptalipopeptides, which differ only in their fatty acid chains [145]. The gene clusters of the Bacillus LPs encoding the surfactin, fengycin, iturin and kurstakin families have been described and summarized in a number of recent reviews [6, 11, 136, 145]. Cerexins are linear LPs with strong antimicrobial activity against S. aureus and Streptococcus pneumoniae [146].…”

“…Paenibacillus now are found to produce a large number of LPs [136]. Polymyxins are cyclic cationic LPs which contain the non-proteogenic amino acid 2, 4-diaminobutyric acid contributing to the overall positive charge of the cationic LPs, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria by acting on their membranes.…”

Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

“…The product homologues and specific applications of top lipopeptide-elaborating bacteria Bacillus and Paenibacillus spp. been reviewed in many insightful reviews Aleti et al 2015). The synergistic effect of lipopeptides with colistin (polymyxin E) in inhibition of multidrug-resistant (MDR) Acinetobacter baumannii has been reviewed (Claeys et al 2014).…”