Omics-based natural product discovery and the lexicon of genome mining

Abstract

Genome sequencing and the application of omic techniques are driving many important advances in the field of microbial natural products research. Despite these gains, there remain aspects of the natural product discovery pipeline where our knowledge remains poor. These include the extent to which biosynthetic gene clusters are transcriptionally active in native microbes, the temporal dynamics of transcription, translation, and natural product assembly, as well as the relationships between small molecule production and detection. Here we touch on a number of these concepts in the context of continuing efforts to unlock the natural product potential revealed in genome sequence data and discuss nomenclatural issues that warrant consideration as the field moves forward.

Natural Products from Actinobacteria Associated with Fungus-Growing Termites

“…The revolutionary developments in genome sequencing and analytical technologies in the last decade have dramatically changed the field of natural product discovery [ 4 ]. Particularly, ecology-driven natural product discovery approaches including the chemical analyses of symbiotic microorganisms, in combination with omics-based dereplication strategies, have become highly efficient approaches to identify new natural products with unique chemical scaffolds and bioactivities [ 5 , 6 , 7 , 8 ]. Most notably, the analysis of insect-microbe symbioses, and more specifically insect-Actinobacteria interactions, have been the focus of a series of recent natural product discovery studies, as bacterial symbionts are required to communicate with the host or participate in host defense using small molecules.…”

Genome Mining as New Challenge in Natural Products Discovery

“…Using different algorithms that compare the new genetic information with 57 virtual enzymatic reactions (such as adenylation, acyltransferase, and acyl-adenylating), this approach provides the possibility of obtaining a correspondence between known natural drugs and possible new ones [20]. (iii) "Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters" (IMG/ABC) [21], launched in 2015, is a large open web database of known predicted microbial BGCs able to associate BGCs with secondary metabolites (SMs) and analyze both BGCs and SMs. In this way, it offers the ability of finding similar function between BGCs present in database and BGCs to be identified [22].…”

“…Genome mining aims at predicting the genes that encode for new natural compounds of biotechnological interest by using several bioinformatic approaches [21]. The importance of genome mining is based on the urgent need to discover new drug entities due to the increased incidence of severe diseases (such as cancer) and the reduced efficacy of existing drugs [27].…”

Synthetic Biology Tools for Novel Secondary Metabolite Discovery in Streptomyces

“…In this review, we summarized a synthetic biology strategy to produce novel secondary metabolites in Streptomyces. Accumulation of genetic information and SM-BGCs aided by recent advances in Next-Generation Sequencing (NGS) has revealed the enormous potential of Streptomyces as a reservoir for novel bioactive compounds and is far outpacing our capacity to explore SM-BGCs and their products [129]. To fully harness Streptomyces' ability to produce valuable secondary metabolites, rational design and efficient synthetic biology tools for Streptomyces are essential.…”