Journal
PHYTOCHEMISTRY
Volume 193, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phytochem.2021.112983
Keywords
Kappaphycus alvarezii (Doty) LMLiao; Solieriaceae; Heterotrophic Bacillus amyloliquefaciens (ex. Fukumoto) Priest et al.; Macrobrevins; Antibacterial; Trans-AT polyketide synthase
Categories
Funding
- Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), India [MBT/HLT/SUB23]
- ICAR-CMFRI
- Faculty of Marine Sciences, Lakeside Campus, Cochin University of Science and Technology
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This article reports the isolation of a bacterium strain MTCC 12713 from Marine heterotrophs, which shows promising antimicrobial activities against several drug-resistant pathogens. The study also discovers the biosynthetic potential of this bacterium in producing macrobrevin analogues, which have strong antibacterial activities.
Marine heterotrophs are treasured bio-resources of antimicrobial metabolites, and herein we report the biosynthetic potential of Bacillus amyloliquefaciens (ex. Fukumoto) Priest et al. (Bacillaceae) strain MTCC 12713 isolated from an intertidal macroalga Kappaphycus alvarezii (Doty) L.M.Liao (Rhodophyta: Solieriaceae). The bacterium showed promising biological activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Genome mining of B. amyloliquefaciens MTCC 12713 predicted the gene clusters coding for biosynthesis of antibacterial metabolites. Bioactivity-guided purification was directed to isolate four homologous members of trans-acyltransferase polyketide synthase-derived antibiotics, which were classified as macrobrevin analogues. The compounds exhibited antibacterial activities against nosocomial pathogens, for example, methicillin-resistant S. aureus, vancomycin-resistant E. faecalis, Klebsiella pneumoniae and Pseudomonas aeruginosa with a range of MIC values from 1.56 to 6.25 mu g/mL, although standard antibiotic chloramphenicol was active at 6.25-12.5 mu g/mL. Conspicuously, the macrobrevin compound encompassing hexahydro-41-hydroxy-macrobrevin-31-acetate functionality, displayed considerably greater antagonistic activities against methicillin-resistant S. aureus, vancomycin-resistant E. faecalis, Vibrio parahaemolyticus, P. aeruginosa, K. pneumoniae, and Streptococcus pyogenes (MIC 1.56 mu g/mL) compared to the positive controls and other macrobrevin analogues. Trans-AT polyketide synthase-stimulated biosynthetic pathway of macrobrevin compounds, through repetitive decarboxylative Claisen condensation between acetyl-S-KS domain and malonateS-ACP units could corroborate the structural elucidation. In the genome mining study, among the 34 biosynthetic gene clusters, a hybrid trans-acyltransferase (trans-AT) pks/nrps gene cluster, which extends up to similar to 81 Kb, was recognized in the genome of B. amyloliquefaciens MTCC 12713. The pks/nrps cluster revealed 46% similarity to trans-AT PKS-derived macrobrevin isolated from a mesophilic bacterium Brevibacillus sp. Leaf182 associated with the phyllosphere of the wild-type genotype of Arabidopsis thaliana. The binding positions for macrobrevins with S. aureus peptide deformylase showed docking score of larger than 14 kcal/mol, which was considerably greater than macrolactin N and actinonin (<10 kcal/mol). These present findings documented that the marine heterotrophic B. amyloliquefaciens MTCC 12713 could be used to develop prospective antibacterial agents belonging to macrobrevin analogues for biotechnological and pharmaceutical applications.
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