Unusual Biosynthesis and Structure of Locillomycins from Bacillus subtilis 916

Abstract

In the competition for nutrients, members of the Bacillus genus often produce a vast array of biologically active molecules that potentially inhibit the development of competing organisms. The Gram-positive bacterium Bacillus subtilis has an average of 4 to 5% of its genome devoted to antibiotic synthesis and is able to produce more than two dozen antibiotics with an amazing variety of structures (1). Many of these compounds, which have a peptide origin, are synthesized either ribosomally or nonribosomally. Among the nonribosomally generated amphipathic cyclic lipopeptides, surfactins, iturins, and fengycins have well-recognized potential applications in biotechnology and biopharmaceutical products due to their antagonistic activities and surfactant properties (2, 3). Furthermore, the mechanisms behind the observed biocontrol efficacy of different Bacillus strains have also been well described (4-6). Lipopeptides are able to induce systemic resistance in plants and to facilitate the multicellular behaviors of the producing strains, such as swarming motility, biofilm formation, and colony morphology (5-7).Surfactins, iturins, and fengycins are synthesized by nonribosomal peptide synthetases (NRPSs) which exhibit a distinct modular architecture (2, 8-10). A module is typically composed of three core domains, with each domain responsible for a certain biochemical reaction (11). Specifically, the amino acid adenylation domain (A domain) controls the entry of substrates into the peptide structure by recognizing and activating a specific amino acid. The thiolation domain (T domain), also referred to as the peptidyl carrier protein (PCP), contains an invariant serine residue which is essential for the binding of a 4=-phosphopantetheine cofactor. The N-terminal condensation domain (C domain) is required for the coupling of two consecutively bound amino acids (12, 13). These three domains constitute a minimal elongation module, the basic repetitive unit of a multimodular NRPS. Furthermore, modules can be supplemented with domains that catalyze modifications of the activated amino acid, such as N-methylation and epimerization. In some cases, when the first module of an NRPS complex lacks a C domain, the last module contains a termination thioesterase domain (TE domain) to release the end product (14). The order and specificity of the modules within the protein template determine the sequence of the product (for type A, linear NRPSs) (8, 11). Genetic and biochemical analyses have revealed that the modular arrangement of most lipopeptide synthetases is colinear with the amino acid sequences of lipopeptides (1, 2). This assembly line arrangement of the conserved catalytic modules and domains provides the means to construct hybrid NRPSs for use in the synthesis of new lipopeptide compounds (15-18). The prospect of creating numerous bioactive lipopeptides by engineering existing lipopeptide synthetases has stimulated the search for new NRPSs responsible for lipopeptide synthesis (19-24).To date, only two reported kinds of bios...

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

“…Kurstakins and cerexins are isolated and identified from B. thuringiensis and B. cereus strains before, respectively [146, 147]. Locillomycins (locillomycin A, B, and C derivatives), a novel family of cyclic lipopeptides active against bacteria and viruses produced by B. subtilis 916 [148, 149], include a unique nonapeptide sequence and macrocyclization. The locillomycin biosynthetic gene cluster encodes four proteins (LocA, LocB, LocC, and LocD) that form a hexamodular NRPS to biosynthesize cyclic nonapeptides.…”

Overview of the Antimicrobial Compounds Produced by Members of the Bacillus subtilis Group

“…, herpes simplex or porcine epidemic diarrhea viruses). They also inhibit pathogenic bacteria such as Legionella pneumophila , Listeria monocytogenes , R. solanacearum or X. oryzae (Naruse et al, 1990; Yakimov et al, 1995; Sabaté and Audisio, 2013; Loiseau et al, 2015; Luo et al, 2015). However, some surfactins are able to control important fungal plant and human pathogens such as Botrytis cinerea, Candida albicans, F. oxysporum or Rhizoctonia solani (Jenny et al, 1991; Lee et al, 2007; Qi et al, 2010; Dimkić et al, 2013; Romano et al, 2013).…”

Plipastatin A1 produced by a marine sediment-derived Bacillus amyloliquefaciens SH-B74 contributes to the control of gray mold disease in tomato

“…The major lipopeptides produced by Bacillus sp. are iturins, fengycins, surfactins, kurstakins, and locillomycins (Ongena and Jacques 2008;Hathout et al 2000;Luo et al 2015). The chemical structure of a cyclic lipopeptide composes of a peptidic backbone and a fatty acid tail, and the amino acid sequence is generally cyclized.…”