Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 7 Number 1 2024
REVIEWS (Open Access)
Unlocking Nature’s Pharmacy: Exploring Secondary Metabolites Through Genome Mining and Advanced Cultivation Strategies
Sawsan S. Al-Rawi1*, Ahmad Hamdy Ibrahim2
Microbial Bioactives 7 (1) 1-8 https://doi.org/10.25163/microbbioacts.7110657
Submitted: 27 January 2024 Revised: 11 March 2024 Accepted: 19 March 2024 Published: 21 March 2024
Abstract
Microorganisms represent an immense reservoir of chemically diverse secondary metabolites (SMs), which are indispensable for medicine, agriculture, and biotechnology. Traditional culture-based screening approaches, often referred to as "grind and find," have historically yielded the majority of clinically relevant antibiotics, antitumor agents, and immunosuppressants. However, these methods face substantial limitations, including the “great plate count anomaly,” high rediscovery rates, and the inability to access transcriptionally silent or cryptic biosynthetic gene clusters (BGCs). Recent advances in genome mining, metagenomics, and bioinformatics have transformed natural product discovery, enabling researchers to explore the largely uncultured “microbial dark matter.” Tools such as antiSMASH, ClusterFinder, and PRISM allow high-confidence identification and chemical prediction of BGCs from environmental DNA, while approaches like iChip cultivation, OSMAC strategies, and co-culture techniques facilitate activation of cryptic pathways. Marine and host-associated microbiomes have emerged as particularly rich sources of novel bioactive compounds, often yielding unique chemical scaffolds with potent antimicrobial or anticancer activity. This systematic review and meta-analysis synthesize data from contemporary studies on BGC detection, cultivation innovations, and metabolite characterization, highlighting the impact of integrative genomics-metabolomics pipelines on SM discovery. Quantitative analyses demonstrate that targeted genome-guided strategies yield compounds with higher bioactivity and lower rediscovery rates compared to traditional screening. By bridging genomic insights with functional metabolite assays, these approaches offer a roadmap for sustainable drug discovery and biotechnological innovation.
Keywords: Secondary metabolites, biosynthetic gene clusters, microbial dark matter, genome mining, metagenomics, metabolomics, OSMAC, iChip
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