Abstract
Microorganisms in the environment can produce a diverse range of secondary metabolites (SM), which are also known as natural products. Bioactive SMs have been crucial in the development of antibiotics and can also act as useful compounds in the biotechnology industry. These natural products are encoded by an extensive range of biosynthetic gene clusters (BGCs). The developments in omics technologies and bioinformatic tools are contributing to a paradigm shift from traditional culturing and screening methods to bioinformatic tools and genomics to uncover BGCs that were previously unknown or transcriptionally silent. Natural product discovery using bioinformatics and omics workflow in the environment has demonstrated an extensive distribution of BGCs in various environments, such as soil, aquatic ecosystems and host microbiome environments. Computational tools provide a feasible and culture-independent route to find new secondary metabolites where traditional approaches cannot. This review will highlight some of the advances in the approaches, primarily bioinformatic, in identifying new BGCs, especially in environments where microorganisms are rarely cultured. This has allowed us to tap into the huge potential of microbial dark matter.
Highlights
Microorganisms in the environment can produce a wide range of secondary metabolites (SM)
Moore et al successfully extended this method to the heterologous expression of biosynthetic gene clusters (BGCs) in Bacillus subtilis and Escherichia coli, which subsequently led to the discovery of a distinct group of thiotetronic acid natural products by combining this approach with targeted genome mining [32,33]
This study demonstrates the importance for integrating novel laboratory techniques alongside computational tools as this will enable new microorganisms to be isolated, with the potential to extract new natural products and reconstruct their metabolic pathways
Summary
Microorganisms in the environment can produce a wide range of secondary metabolites (SM). SMs can act as antibiotics, antitumor agents, cholesterol-lowering agents and so on [1] These natural products have been critical in the development of therapeutics in medicine as it has been reported that approximately 70% of the anti-infective drugs are derived from natural products in the environment [2]. The developments in sequencing technology and readily available bioinformatic pipelines have enabled large quantities of BGCs to be mined from environmental microorganisms without having to culture them and test their bioactivity [9] These tools provide an incredible opportunity to elucidate the secondary metabolism properties of microbial dark matter, which is the uncultured majority of microbial diversity. The purpose of this review is to highlight various methods used to identify BGCs in the environment and provide examples of how recent studies have explored the genetic basis for novel natural product synthesis, which have wide ranging medical and industrial applications
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