Classification and Multifaceted Potential of Secondary Metabolites Produced by Bacillus subtilis Group: A Comprehensive Review

Abstract

Despite their remarkable biosynthetic potential, Bacillus subtilis have been widely overlooked. However, their capability to withstand harsh conditions (extreme temperature, Ultraviolet (UV) and γ-radiation, and dehydration) and the promiscuous metabolites they synthesize have created increased commercial interest in them as a therapeutic agent, a food preservative, and a plant-pathogen control agent. Nevertheless, the commercial-scale availability of these metabolites is constrained due to challenges in their accessibility via synthesis and low fermentation yields. In the context of this rising in interest, we comprehensively visualized the antimicrobial peptides produced by B. subtilis and highlighted their prospective applications in various industries. Moreover, we proposed and classified these metabolites produced by the B. subtilis group based on their biosynthetic pathways and chemical structures. The biosynthetic pathway, bioactivity, and chemical structure are discussed in detail for each class. We believe that this review will spark a renewed interest in the often disregarded B. subtilis and its remarkable biosynthetic capabilities.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice

“…Bacillus subtilis is one of the main sources of probiotics and is classified as GRAS (Generally Recognized as Safe) by the US Food and Drug Administration (FDA). This organism has remarkable biosynthetic potential [ 6 ] and secretes a variety of secondary metabolites such as enzymes and lipopeptides that exhibit broad-spectrum antimicrobial [ 7 ], anticancer [ 8 ], antinematicidal activities [ 9 ], and immune activation in plants [ 10 ] and animals ( 11 – 13 ). Lipopeptides act as immunomodulators by interacting with pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), expressed on antigen-presenting cells (macrophages and dendritic cells) to activate immune functions [ 14 ].…”

Bacillus-based biocontrol beyond chemical control in central Africa: the challenge of turning myth into reality

“…Cyclic lipopeptides are a group of compounds with a fatty acid and peptide moiety that are produced via the non-ribosomal pathway involving a multi-modular enzyme complex ( Iqbal et al., 2023 ). This machinery gives rise to a large chemical diversity with different structures, based on their amino acid sequence or on the length of the fatty acid chain.…”

“…Polyketides are bioactive metabolites synthetized via pathways catalyzed either by the polyketide synthases (difficidins and macrolactins) or by the hybrid polyketide synthases/non-ribosomal peptide synthetases (bacillaene) and are structurally composed of an alternation of polyenes and carbonyl groups ( Iqbal et al., 2023 ). They retain consistent antibacterial activity against several phytopathogens either by interfering with protein synthesis or by damaging the bacterial cell wall ( Fazle Rabbee and Baek, 2020 ; Miao et al., 2023 ; Zhang N. et al., 2023 ).…”

Targeted Isolation of Antibiofilm Compounds from Halophytic Endophyte Bacillus velezensis 7NPB-3B Using LC-HR-MS-Based Metabolomics

“…Among various biocontrol agents, Bacillus sp. has demonstrated strong abilities to restrict microbial pathogens of various niches by the production of hydrolytic enzymes, peptides, and polyketides [ 6 ]. B. velezensis is a recently classified species of the genus Bacillus [ 7 , 8 ] and is reported to exhibit antifungal activity, plant growth promotion properties, dye detoxification, and keratinolytic, dehairing, and proteolytic actions.…”