Advanced techniques can accelerate the pace of natural product discovery from microbes, which has been lagging behind the drug discovery era. Therefore, the present review article discusses the various interdisciplinary and cutting-edge techniques to present a concrete strategy that enables the high-throughput screening of novel natural compounds (NCs) from known microbes. Recent bioinformatics methods revealed that the microbial genome contains a huge untapped reservoir of silent biosynthetic gene clusters (BGC). This article describes several methods to identify the microbial strains with hidden mines of silent BGCs. Moreover, antiSMASH 5.0 is a free, accurate, and highly reliable bioinformatics tool discussed in detail to identify silent BGCs in the microbial genome. Further, the latest microbial culture technique, HiTES (high-throughput elicitor screening), has been detailed for the expression of silent BGCs using 500-1000 different growth conditions at a time. Following the expression of silent BGCs, the latest mass spectrometry methods are highlighted to identify the NCs. The recently emerged LAESI-IMS (laser ablation electrospray ionization-imaging mass spectrometry) technique, which enables the rapid identification of novel NCs directly from microtiter plates, is presented in detail. Finally, various trending 'dereplication' strategies are emphasized to increase the effectiveness of NC screening.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11243205 | PMC |
| http://dx.doi.org/10.3390/molecules29133237 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mining Silent Biosynthetic Gene Clusters for Natural Products in Filamentous Fungi.
Chem Biodivers
January 2025
Zhejiang University, Polytechnic Institute, 866 Yuhangtang Road, Hangzhou, CHINA.
Filamentous fungi are of great interest due to their powerful metabolic capabilities and potentials to produce abundant various secondary metabolites as natural products (NPs), some of which have been developed into pharmaceuticals. Furthermore, high-throughput genome sequencing has revealed tremendous cryptic NPs underexplored. Based on the development of in silico genome mining, various techniques have been introduced to rationally modify filamentous fungi,awakening the silent biosynthetic gene clusters (BGCs) and visualizing the NPs originally cryptic.
View Article and Find Full Text PDFUnconventional approaches for the induction of microbial natural products.
J Appl Microbiol
January 2025
School of Computing, Engineering & Physical Sciences, University of the West of Scotland, High Street, Paisley PA1 2BE, Scotland, UK.
Expansion of the microbial drug discovery pipeline has been impeded by a limited and skewed appreciation of the microbial world and its full chemical capabilities and by an inability to induce silent biosynthetic gene clusters (BGCs). Typically, these silent genes are not expressed under standard laboratory conditions, instead requiring particular interventions to activate them. Genetic, physical, and chemical strategies have been employed to trigger these BGCs, and some have resulted in the induction of novel secondary metabolites.
View Article and Find Full Text PDFCurrent Knowledge on CRISPR Strategies Against Antimicrobial-Resistant Bacteria.
Antibiotics (Basel)
November 2024
Department of Chemical Engineering and Environmental Technology, School of Industrial Engineering, University of Valladolid, Paseo Prado de la Magdalena 3-5, 47011 Valladolid, Spain.
CRISPR/Cas systems have emerged as valuable tools to approach the problem of antimicrobial resistance by either sensitizing or lysing resistant bacteria or by aiding in antibiotic development, with successful applications across diverse organisms, including bacteria and fungi. CRISPR/Cas systems can target plasmids or the bacterial chromosome of AMR-bacteria, and it is especially necessary to have an efficient entry into the target cells, which can be achieved through nanoparticles or bacteriophages. Regarding antibiotic development and production, though the use of CRISPR/Cas in this field is still modest, there is an untapped reservoir of bacterial and fungal natural products, with over 95% yet to be characterized.
View Article and Find Full Text PDFGenome mining and biosynthetic pathways of marine-derived fungal bioactive natural products.
Front Microbiol
December 2024
School of Bioengineering, Zunyi Medical University, Zhuhai, China.
Marine fungal natural products (MFNPs) are a vital source of pharmaceuticals, primarily synthesized by relevant biosynthetic gene clusters (BGCs). However, many of these BGCs remain silent under standard laboratory culture conditions, delaying the development of novel drugs from MFNPs to some extent. This review highlights recent efforts in genome mining and biosynthetic pathways of bioactive natural products from marine fungi, focusing on methods such as bioinformatics analysis, gene knockout, and heterologous expression to identify relevant BGCs and elucidate the biosynthetic pathways and enzyme functions of MFNPs.
View Article and Find Full Text PDFHarnessing the microbial interactions from phyllosphere for natural product discovery.
Synth Syst Biotechnol
November 2024
College of Life Science and Technology & Xinjiang Production & Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim University, Alar, 843300, Xinjiang, People's Republic of China.
Article Synopsis
- * This study proposes a new strategy to activate these silent BGCs by utilizing the interactions between different microbial neighbors in a microbiota.
- * The research involved screening microbial isolates from the Luobuma phyllosphere, leading to the discovery of significant metabolic variations and the identification of resistomycin, a bactericidal agent, from co-cultured organisms.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!