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Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotroph be the alternatives?
Appl Microbiol Biotechnol. 2020 Aug; 104(16):7117-7130.AM

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. Key Points •Three antibacterial bacvalactones were identified from the symbiotic bacterium. •The symbiotic bacterial genome was explored to identify the biosynthetic gene clusters. •Trans-AT pks-assisted mln biosynthetic pathway of the macrocyclic lactone was proposed. •In silicomolecular interactions of the bacvalactones with S. aureus PDF were analyzed.

Authors+Show Affiliations

Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India. kajal_cmfri@yahoo.com.Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India. Faculty of Marine Sciences, Lakeside Campus, Cochin University of Science and Technology, Cochin, Kerala State, India.Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India.Crustacean Fisheries Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32621124

Citation

Chakraborty, Kajal, et al. "Moving Away From Traditional Antibiotic Treatment: Can Macrocyclic Lactones From Marine Macroalga-associated Heterotroph Be the Alternatives?" Applied Microbiology and Biotechnology, vol. 104, no. 16, 2020, pp. 7117-7130.
Chakraborty K, Kizhakkekalam VK, Joy M, et al. Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotroph be the alternatives? Appl Microbiol Biotechnol. 2020;104(16):7117-7130.
Chakraborty, K., Kizhakkekalam, V. K., Joy, M., & Chakraborty, R. D. (2020). Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotroph be the alternatives? Applied Microbiology and Biotechnology, 104(16), 7117-7130. https://doi.org/10.1007/s00253-020-10658-0
Chakraborty K, et al. Moving Away From Traditional Antibiotic Treatment: Can Macrocyclic Lactones From Marine Macroalga-associated Heterotroph Be the Alternatives. Appl Microbiol Biotechnol. 2020;104(16):7117-7130. PubMed PMID: 32621124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moving away from traditional antibiotic treatment: can macrocyclic lactones from marine macroalga-associated heterotroph be the alternatives? AU - Chakraborty,Kajal, AU - Kizhakkekalam,Vinaya Kizhakkepatt, AU - Joy,Minju, AU - Chakraborty,Rekha Devi, Y1 - 2020/07/03/ PY - 2020/03/12/received PY - 2020/04/29/accepted PY - 2020/04/17/revised PY - 2020/7/6/pubmed PY - 2020/7/6/medline PY - 2020/7/5/entrez KW - Antibacterial activity KW - Bacillus amyloliquefaciens MTCC 12716 KW - Intertidal red algae KW - Macrocyclic lactone KW - Peptide deformylase inhibitors KW - Polyketide synthase SP - 7117 EP - 7130 JF - Applied microbiology and biotechnology JO - Appl. Microbiol. Biotechnol. VL - 104 IS - 16 N2 - 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. Key Points •Three antibacterial bacvalactones were identified from the symbiotic bacterium. •The symbiotic bacterial genome was explored to identify the biosynthetic gene clusters. •Trans-AT pks-assisted mln biosynthetic pathway of the macrocyclic lactone was proposed. •In silicomolecular interactions of the bacvalactones with S. aureus PDF were analyzed. SN - 1432-0614 UR - https://www.unboundmedicine.com/medline/citation/32621124/Moving_away_from_traditional_antibiotic_treatment:_can_macrocyclic_lactones_from_marine_macroalga-associated_heterotroph_be_the_alternatives L2 - https://dx.doi.org/10.1007/s00253-020-10658-0 DB - PRIME DP - Unbound Medicine ER -
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