Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotrophy be the alternatives?

Chakraborty, Kajal and Vinaya, K K and Joy, Minju and Chakraborty, Rekha D (2020) Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotrophy be the alternatives? Applied Microbiology and Biotechnology, 104. pp. 7117-7130.

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Abstract

Intertidal red algae Hypnea valentiae associated Bacillus amyloliquefaciens MTCC 12716 revealed potential inhibitory effects on the growth of drug-resistant pathogens. In the genome of B. amyloliquefaciens MTCC 12716, biosynthetic gene clusters encoding antibacterial metabolites were predicted, which might be expressed and contributed to the broad-spectrum anti-infective activity. Three homologue members of the 24-membered macrocyclic lactone family, named as bacvalactones 1–3 bearing 13-O-ethyl (1); 15-O-furanyl-13-O-isobutyl-7-O-propyl-propanoate (2); and 15-O-furanyl-13-O-isobutyl-7-O-propyl-propanoate-7,24-dimethyl (3) functionalities, were acquired through bioactivity-guided purification. The macrocyclic lactones displayed bactericidal activity against opportunistic pathogens causing nosocomial infections, for instance, methicillin–resistant Staphylococcus aureus (MRSA), vancomycin–resistant Enterococcus faecalis (VREfs), and multidrug-resistant strains of Pseudomonas aeruginosa and Klebsiella pneumonia with MIC ≤ 3.0 μg/mL, whereas standard antibiotics ampicillin and chloramphenicol were active only at concentrations of ≥ 6.25 mg/mL. The biosynthetic pathway of macrocyclic lactones that are generated by trans-AT polyketide synthases through stepwise extension of an acetyl starter unit by eleven sequential Claisen condensations with malonyl-CoA was established, and the structures were correlated with the gene organization of the mln operon, which encompasses nine genes mln A-I (approximately 47 kb in size). The best binding poses for each compounds (1–3) with Staphylococcus aureus peptide deformylase (SaPDF) unveiled docking scores (≥ 9.70 kcal/mol) greater than that of natural peptide deformylase inhibitors, macrolactin N and actinonin (9.14 and 6.96 kcal/mol, respectively), which supported their potential in vitro bioactivities. Thus, the present work demonstrated the potential of macrocyclic lactone for biotechnological and pharmaceutical applications against emerging multidrug-resistant pathogens.

Item Type:	Article
Uncontrolled Keywords:	Bacillus amyloliquefaciens MTCC 12716; Intertidal red algae; Antibacterial activity; Macrocyclic lactone; Peptide deformylase inhibitors; Polyketide synthase
Subjects:	Biochemistry > Bioprospecting Biochemistry > Bioactive compounds Biochemistry
Divisions:	CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division Subject Area > CMFRI > CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division Subject Area > CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division
Depositing User:	Arun Surendran
Date Deposited:	23 Jul 2020 09:13
Last Modified:	23 Jul 2020 09:13
URI:	http://eprints.cmfri.org.in/id/eprint/14400

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