Microbial Natural Products in the Post-Antibiotic Era: Marine Biodiversity, Genome Mining, and Strategies to Unlock Cryptic Bioactive Compounds

Normurodova Kunduz Togaevna; Vakhabov Abdurasul Khakimovich; Tashmukhamedova Shokhista Sabirovna

doi:10.25163/microbbioacts.4110714

Microbial Bioactives

Microbial Bioactives | Online ISSN 2209-2161

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Volume 4 Number 1 2021

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Microbial Natural Products in the Post-Antibiotic Era: Marine Biodiversity, Genome Mining, and Strategies to Unlock Cryptic Bioactive Compounds

Abstract 1. Introduction 2. Materials and Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

Normurodova Kunduz Togaevna ¹*, Vakhabov Abdurasul Khakimovich¹, Tashmukhamedova Shokhista Sabirovna ¹

+ Author Affiliations

Microbial Bioactives 4 (1) 1-8 https://doi.org/10.25163/microbbioacts.4110714

Submitted: 26 July 2021 Revised: 17 September 2021 Accepted: 27 September 2021 Published: 29 September 2021

Abstract

Microbial natural products are a cornerstone of drug discovery, offering structurally diverse molecules with potent biological activities. Historically, soil-derived Actinobacteria have been the primary source of clinically relevant antibiotics, yet rising multidrug resistance and the redundancy of terrestrial compounds have necessitated exploration of alternative environments, particularly marine ecosystems. Marine Actinomycetes and fungi have emerged as prolific producers of novel metabolites, including compounds with antibacterial, antifungal, anticancer, and anti-inflammatory activities. Cyanobacteria and microalgae further expand the chemical repertoire by producing unique bioactive metabolites and high-value nutraceuticals. Despite this potential, the majority of microbial biodiversity remains uncultured due to the “Great Plate Count Anomaly,” and many biosynthetic gene clusters are silent under standard laboratory conditions. Innovative approaches such as One Strain Many Compounds (OSMAC), co-cultivation, genome mining, metabologenomics, and molecular networking have improved access to these cryptic metabolites. Additionally, in situ cultivation techniques, high-throughput screening, and synthetic biology enable the discovery and optimization of bioactive molecules with therapeutic potential. This systematic review and meta-analysis synthesize current literature to evaluate the strategies used in microbial natural product discovery, highlighting both ecological and technological approaches that maximize chemical diversity. By integrating cultivation-based, genomic, and bioinformatic methodologies, researchers can systematically exploit microbial resources, reduce redundancy, and accelerate the identification of novel compounds. The findings underscore the immense untapped potential within microbial communities and provide a roadmap for future biodiscovery initiatives aimed at combating multidrug-resistant pathogens and advancing therapeutic development.

Keywords: Microbial natural products; marine Actinomycetes; fungi; cyanobacteria; drug discovery; biosynthetic gene clusters; OSMAC; co-cultivation; genome mining; metabolomics.

References

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Microbial Bioactives

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Microbial Natural Products in the Post-Antibiotic Era: Marine Biodiversity, Genome Mining, and Strategies to Unlock Cryptic Bioactive Compounds

Abstract

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