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Review
. 2021 May 17;26(10):2977.
doi: 10.3390/molecules26102977.

Strategies for Natural Products Discovery from Uncultured Microorganisms

Khorshed Alam  1 , Muhammad Nazeer Abbasi  1 , Jinfang Hao  1 , Youming Zhang  1 , Aiying Li  1
Affiliations
Review

Strategies for Natural Products Discovery from Uncultured Microorganisms

Khorshed Alam et al. Molecules. .

Abstract

Microorganisms are highly regarded as a prominent source of natural products that have significant importance in many fields such as medicine, farming, environmental safety, and material production. Due to this, only tiny amounts of microorganisms can be cultivated under standard laboratory conditions, and the bulk of microorganisms in the ecosystems are still unidentified, which restricts our knowledge of uncultured microbial metabolism. However, they could hypothetically provide a large collection of innovative natural products. Culture-independent metagenomics study has the ability to address core questions in the potential of NP production by cloning and analysis of microbial DNA derived directly from environmental samples. Latest advancements in next generation sequencing and genetic engineering tools for genome assembly have broadened the scope of metagenomics to offer perspectives into the life of uncultured microorganisms. In this review, we cover the methods of metagenomic library construction, and heterologous expression for the exploration and development of the environmental metabolome and focus on the function-based metagenomics, sequencing-based metagenomics, and single-cell metagenomics of uncultured microorganisms.

Keywords: eDNA; environmental metabolome; extreme ecosystem; heterologous expression; metagenomics; microbial dark matter; natural products; single cell sequencing; uncultured microorganisms.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphical representation of approaches for NP discovery from environmental samples. Enrichment and evaluation of environmental samples are necessary steps prior to metagenomics analysis. Function-based metagenomics analysis includes library construction, heterologous expression, and function-based screening. Sequencing-based metagenomics analysis requires eDNA sequencing, DNA synthesis and assembly, and heterologous expression of target clones. Single-cell metagenomics analysis includes cell sorting, single cell genomic DNA amplification, genome sequencing, and DNA synthesis and assembly of NP biosynthetic gene clusters (BGGs) of interest, then expression and chemical identification.
Figure 2
Figure 2
Natural products discovered by function-based screening of metagenomic-library clones.
Figure 3
Figure 3
Natural products identified/studied by sequencing-based approaches.
See this image and copyright information in PMC

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