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

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Relation http://eprints.cmfri.org.in/14400/
https://link.springer.com/article/10.1007/s00253-020-10658-0
 
Title Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotrophy be the alternatives?
 
Creator Chakraborty, Kajal
Vinaya, K K
Joy, Minju
Chakraborty, Rekha D
 
Subject Bioprospecting
Bioactive compounds
Biochemistry
 
Description 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.
 
Date 2020
 
Type Article
PeerReviewed
 
Format text
 
Language en
 
Identifier http://eprints.cmfri.org.in/14400/1/Applied%20Microbiology%20and%20Biotechnology_2020_Kajal%20Chakraborty.pdf
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.