Targeted metagenomics as a tool to tap into marine natural product diversity for the discovery and production of drug candidates

摘要: Microbial natural products exhibit immense structural diversity and complexity have captured the attention of researchers for several decades. They been explored a wide spectrum applications, most noteworthy being their prominent role in medicine, versatility expands to application as drugs many diseases. Accessing unexplored environments harboring unique microorganisms is expected yield novel bioactive metabolites with distinguishing functionalities, which can be supplied starved pharmaceutical market. For this purpose oceans turned out an attractive productive field. Owing enormous biodiversity marine microorganisms, well growing evidence that previously isolated from invertebrates algae are actually produced by associated bacteria, interest has intensified. Since majority uncultured, metagenomic tools required exploit untapped biochemistry. However, after years employing metagenomics drug discovery, new vastly under-represented. While plethora product biosynthetic genes clusters reported, only minor number potential therapeutic compounds resulted through functional screening. This review explores specific obstacles led low success rate. In addition typical problems encountered traditional metagenomic-based screens biocatalysts, there limitations particular drug-like metabolites. We also present how targeted function-guided strategies, modern, multi-disciplinary approaches yielded some exciting discoveries attributed uncultured bacteria. These set stage progressing production candidates bacteria pre-clinical clinical development.