Difficidin class of polyketide antibiotics from marine macroalga-associated Bacillus as promising antibacterial agents

Chakraborty, Kajal and Vinaya, K K and Joy, Minju and Dhara, Subhajit (2021) Difficidin class of polyketide antibiotics from marine macroalga-associated Bacillus as promising antibacterial agents. Applied Microbiology and Biotechnology, 105. pp. 6395-6408.

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    Abstract

    A heterotrophoic Bacillus amyloliquefaciens MTCC12713 isolated from an intertidal macroalga Kappaphycus alverezii displayed promising antibacterial activities against multidrug-resistant bacteria. Genome mining of the bacterium predicted biosynthetic gene clusters coding for antibacterial secondary metabolites. Twenty-one membered macrocyclic lactones, identified as difficidin analogues bearing 6-hydroxy-8-propyl carboxylate, 9-methyl-19-propyl dicarboxylate, 6-methyl-9-propyl dicarboxylate-19-propanone, and (20-acetyl)-6-methyl-9-isopentyl dicarboxylate (compounds 1 through 4) functionalities were purified through bioassay-guided fractionation. The difficidin analogues exhibited bactericidal activities against vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and other drug-resistant strains, such of Klebsiella pneumonia and Pseudomonas aeruginosa with the minimum inhibitory concentration of about 2–9 × 10−3 μM. A plausible enzyme-catalyzed biosynthetic pathway that is generated through addition of acrylyl initiator unit by repetitive decarboxylative Claisen condensation modules with malonate units was recognized, and their structures were corroborated with gene organization of the dif operon, which could comprehend dif A-O (~ 70 kb). Drug-likeness score for 5-ethoxy-28-methyl-(9-methyl-19-propyl dicarboxylate) difficidin (compound 2, 0.35) was greater than those of other difficidin analogues, which corroborated the potential in vitro antibacterial properties of the former. The present study demonstrated the potential of difficidin analogues for pharmaceutical and biotechnological uses against the bottleneck of emergent drug-resistant pathogens.

    Item Type: Article
    Uncontrolled Keywords: Heterotrophic Bacillus amyloliquefaciens MTCC12713; Difficidin analogues; Macrocyclic lactones; Biosynthetic gene clusters; Antibacterial activity; Polyketide synthase
    Subjects: Biochemistry > Bioactive compounds
    Biochemistry
    Algae
    Divisions: CMFRI-Kochi > Marine Biotechnology
    Subject Area > CMFRI > CMFRI-Kochi > Marine Biotechnology
    CMFRI-Kochi > Marine Biotechnology
    Subject Area > CMFRI-Kochi > Marine Biotechnology
    Depositing User: Arun Surendran
    Date Deposited: 30 Aug 2021 05:58
    Last Modified: 30 Aug 2021 05:58
    URI: http://eprints.cmfri.org.in/id/eprint/15233

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