scholarly journals Ribosomally derived lipopeptides containing distinct fatty acyl moieties

2022 ◽  
Vol 119 (3) ◽  
pp. e2113120119
Author(s):  
Florian Hubrich ◽  
Nina M. Bösch ◽  
Clara Chepkirui ◽  
Brandon I. Morinaka ◽  
Michael Rust ◽  
...  
Keyword(s):  
Natural Products ◽  
Cyclic Peptide ◽  
Fatty Acyl ◽  
Antifungal Drugs ◽  
Guided Discovery ◽  
Bacterial Phyla ◽  
Peptide Synthetases ◽  
Antibacterial And Antifungal ◽  
Microbial Natural Products

Lipopeptides represent a large group of microbial natural products that include important antibacterial and antifungal drugs and some of the most-powerful known biosurfactants. The vast majority of lipopeptides comprise cyclic peptide backbones N-terminally equipped with various fatty acyl moieties. The known compounds of this type are biosynthesized by nonribosomal peptide synthetases, giant enzyme complexes that assemble their products in a non–gene-encoded manner. Here, we report the genome-guided discovery of ribosomally derived, fatty-acylated lipopeptides, termed selidamides. Heterologous reconstitution of three pathways, two from cyanobacteria and one from an arctic, ocean-derived alphaproteobacterium, allowed structural characterization of the probable natural products and suggest that selidamides are widespread over various bacterial phyla. The identified representatives feature cyclic peptide moieties and fatty acyl units attached to (hydroxy)ornithine or lysine side chains by maturases of the GCN5-related N-acetyltransferase superfamily. In contrast to nonribosomal lipopeptides that are usually produced as congener mixtures, the three selidamides are selectively fatty acylated with C10, C12, or C16 fatty acids, respectively. These results highlight the ability of ribosomal pathways to emulate products with diverse, nonribosomal-like features and add to the biocatalytic toolbox for peptide drug improvement and targeted discovery.

scholarly journals Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens

2019 ◽  
Vol 19 (28) ◽  
pp. 2567-2578 ◽  
Author(s):  
Rajeev K. Singla ◽  
Ashok K. Dubey
Keyword(s):  
Natural Products ◽  
Mechanism Of Action ◽  
Functional Characterization ◽  
Streptococcus Thermophilus ◽  
Antifungal Drugs ◽  
Bioactive Molecules ◽  
Review Of The Literature ◽  
Candida Spp ◽  
Biofilm Inhibition

Background: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs. Methods: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant. Results: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp. Conclusion: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.

Genome-Guided Discovery of Natural Products and Biosynthetic Pathways from Australia’s Untapped Microbial Megadiversity

2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Sequencing ◽  
Dna Sequences ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Natural Product Biosynthesis ◽  
Guided Discovery ◽  
Biosynthesis Gene ◽  
Microbial Natural Products

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.

scholarly journals A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 20
Author(s):  
Tiago Leão ◽  
Mingxun Wang ◽  
Nathan Moss ◽  
Ricardo da Silva ◽  
Jon Sanders ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Mining ◽  
Gene Clusters ◽  
Microbial Interactions ◽  
Marine Cyanobacteria ◽  
Pharmaceutical Drugs ◽  
Genes Encoding ◽  
Microbial Natural Products

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

scholarly journals Cloning and Characterization of a Cyclic Peptide Synthetase Gene from Alternaria alternata Apple Pathotype Whose Product Is Involved in AM-Toxin Synthesis and Pathogenicity

2000 ◽  
Vol 13 (7) ◽  
pp. 742-753 ◽  
Author(s):  
R. D. Johnson ◽  
L. Johnson ◽  
Y. Itoh ◽  
M. Kodama ◽  
H. Otani ◽  
...  
Keyword(s):  
Alternaria Alternata ◽  
Cyclic Peptide ◽  
Genomic Library ◽  
Disease Symptoms ◽  
Peptide Synthetases ◽  
Peptide Synthetase ◽  
Primary Determinant ◽  
Apple Cultivars ◽  
Alternaria Blotch

Alternaria alternata apple pathotype causes Alternaria blotch of susceptible apple cultivars through the production of a cyclic peptide host-specific toxin, AM-toxin. PCR (polymerase chain reaction), with primers designed to conserved domains of peptide synthetase genes, amplified several products from A. alternata apple pathotype that showed high similarity to other fungal peptide synthetases and were specific to the apple pathotype. Screening of a Lambda Zap genomic library with these PCR-generated probes identified overlapping clones containing a complete cyclic peptide synthetase gene of 13.1 kb in length with no introns. Disruption of this gene, designated AM-toxin synthetase (AMT), by transformation of wild-type A. alternata apple pathotype with disruption vectors resulted in toxin-minus mutants, which were also unable to cause disease symptoms on susceptible apple cultivars. AM-toxin synthetase is therefore a primary determinant of virulence and specificity in the A. alternata apple pathotype/apple interaction.

NMR characterization of complex natural products: Assigning novel, proton-deficient alkaloid scaffolds

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
KR Gustafson ◽  
STS Chan ◽  
D Milanowski
Keyword(s):  
Natural Products ◽  
Nmr Characterization

Bioactivity of Marine Natural Product Xyloketals

2020 ◽  
Vol 17 ◽  
Author(s):  
Biswajit Panda ◽  
Amal Kumar Gooyee
Keyword(s):  
Natural Products ◽  
Marine Natural Product ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Activity Inhibition ◽  
Life Saving ◽  
Behavior Suppression ◽  
Major Emphasis ◽  
Made In

: Oceans can play a major role in supplying life-saving medicines in the world in future. Although considerable progress has been made in finding new medicines from marine sources, large efforts are still necessary to examine such molecules for clinical applications. Xyloketals are an important group of natural products with various powerful and prominent bioactivities such as inhibition of acetylcholine esterase, antioxidant activity, inhibition of L-calcium channels, radicalscavenging behavior, suppression of cell proliferation, reduction of neonatal hypoxic-ischemic brain injury, etc. This review describes the isolation and structural characterization of all xyloketal natural products giving major emphasis on their bioactivity.

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