In today's, society multi-resistant pathogens have become an emerging threat, which makes the search for novel anti-infectives more urgent than ever. A promising class of substances are cyclic lipopeptides like the antifungal jagaricin. Jagaricin is formed by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum. It has shown antifungal activity against human pathogenic fungi like Candida albicans and Aspergillus fumigatus. In addition, jagaricin is nearly non-toxic for plants, which makes it a promising agent for agricultural applications. Cyclic lipopeptides formed by microorganisms originate from their secondary metabolism. This makes it very challenging to determine the inducing factor for product formation, especially for unknown microbial systems like J. agaricidamnosum. In the presented study, a biotechnological process for jagaricin formation was developed, investigating impact factors like the medium, oxygen availability, and phosphate. For this reason, experiments were conducted on microtiter plate, shake flask, and stirred tank bioreactor level. Ultimately, a final maximum jagaricin concentration of 251 mg L (15.5 mg∙g) could be achieved, which is an increase of approximately 458 % in comparison to previous results in standard glucose medium. This concentration allows the production of significantly higher amounts of jagaricin and enables further experiments to investigate the potential of this substance.
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http://dx.doi.org/10.1016/j.jbiotec.2021.06.015 | DOI Listing |
ACS Infect Dis
December 2024
Department of Chemistry, University of Waterloo, 200 University Ave. West, Waterloo, Ontario N2L3G1, Canada.
The calcium-dependent antibiotics (CDAs) are a group of seven closely related membrane-active cyclic lipopeptide antibiotics (cLPAs) first isolated in the early 1980s from the fermentation broth of . Their target was unknown, and the mechanism of action is uncertain. Herein, we report new routes for the synthesis of CDA4b and its analogues, explore the structure-activity relationships at its lipid tail and at positions 3, 9, and 11, and determine the CDAs' lipid target.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.
Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.
J Nat Prod
December 2024
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
New lipodepsipeptides, octaminomycins C and D ( and ), were discovered in an engineered sp. strain overexpressing the LysR transcriptional regulator family. The structures of and were elucidated by comprehensive analysis of their UV, HRMS, and NMR data.
View Article and Find Full Text PDFChem Biodivers
December 2024
Zhejiang University of Technology, School of Pharmaceutical Sciences, Chaowang Road No.18, Not Available, 310014, Hangzhou, CHINA.
Overexpression of a global transcriptional regulator LaeA was performed to awaken cryptic biosynthetic gene clusters (BGCs) in a marine sponge-derived fungus, Aspergillus niger L14, to obtain secondary metabolites (SMs), and resulted in the production of five previously undiscovered SMs in the wild-type strain, including three cyclic lipopeptides aspochracin (1), JBIR-15 (2) and sclerotiotide C (3), and kojic acid (4) and penicillic acid (5). Bioassays revealed that compound 2 displayed promising antimicrobial effects on Candida albicans with a MIC value of 32 µg/mL and 4 exhibited significant antioxidant activity with the similar IC50 value (5 µg/mL) to that of ascorbic acid. Transcriptome analysis results indicated that the overexpression of LaeA in strain L14 remarkably enhanced the expression of genes involved in polyketide synthase-nonribosomal peptide synthetase (PKS/NRPS) hybrids and amino acid metabolism, demonstrating an effective approach for a production of cyclic lipopeptides.
View Article and Find Full Text PDFSci Rep
December 2024
Institute of Biology, Hebei Academy of Sciences, Shijiazhuang, 050081, People's Republic of China.
Spodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S.
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