Frontiers in Clinical Drug Research-Anti Infectives

Author(s): Elena Martinez-Klimova, Sara Centeno-Leija and Sergio Sanchez

DOI: 10.2174/9781681083698117030003

Modern Approaches to Genome Mining for the Development of New Anti-infectives: In Silico Gene Prediction and Experimental Metabolomics

Pp: 3-48 (46)

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Abstract

SHS investigation development is considered from the geographical and historical viewpoint. 3 stages are described. Within Stage 1 the work was carried out in the Department of the Institute of Chemical Physics in Chernogolovka where the scientific discovery had been made. At Stage 2 the interest to SHS arose in different cities and towns of the former USSR. Within Stage 3 SHS entered the international scene. Now SHS processes and products are being studied in more than 50 countries.

Abstract

Genome mining consists in assessing the potential encoded in the genome of microorganisms to produce novel secondary metabolites. Actinobacteria have been reported to hold unexplored potential for the biosynthesis of secondary metabolites, according to the number of gene clusters predicted from recently published genome sequences. This is of significant interest in the area of anti-infectives, since many of the secondary metabolites produced by Actinobacteria have been reported to have antibacterial, antiviral and antitumor properties. The first part of this review offers an overview on in silico bioinformatics software and databases for the prediction of gene clusters involved in the production of putative secondary metabolites. The second part of this review encompasses experimental metabolomics techniques, facilitated by mass spectrometry and quantitative proteomics, all of which have the end goal to identify and characterize secondary metabolites. Examples where metabolomics were associated with computational prediction tools to propose the link between genes and metabolites have been highlighted. As an addition, this review also explores the potential of the OSMAC and co-culturing experimental approaches to induce the expression of silent gene clusters under laboratory conditions. Examples are offered of novel secondary metabolites and gene clusters discovered following a genome mining approach.

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