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Polyketide-derived macrobrevins from marine macroalga-associated Bacillus amyloliquefaciens as promising antibacterial agents against pathogens causing nosocomial infections

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Relation http://eprints.cmfri.org.in/15431/
https://www.sciencedirect.com/science/article/pii/S0031942221003320
https://doi.org/10.1016/j.phytochem.2021.112983
 
Title Polyketide-derived macrobrevins from marine macroalga-associated Bacillus amyloliquefaciens as promising antibacterial agents against pathogens causing nosocomial infections
 
Creator Chakraborty, Kajal
Vinaya, K K
Joy, Minju
 
Subject Bioactive compounds
Biochemistry
Algae
 
Description 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 μg/mL, although standard antibiotic
chloramphenicol was active at 6.25–12.5 μg/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 μg/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 malonate-S-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 ~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 (
 
Publisher Elsevier
 
Date 2021-03-08
 
Type Article
PeerReviewed
 
Format text
 
Language en
 
Identifier http://eprints.cmfri.org.in/15431/1/Phytochemistry_2021_Kajal%20Chakraborty.pdf
Chakraborty, Kajal and Vinaya, K K and Joy, Minju (2021) Polyketide-derived macrobrevins from marine macroalga-associated Bacillus amyloliquefaciens as promising antibacterial agents against pathogens causing nosocomial infections. Phytochemistry, 193. pp. 1-13.