Metabolomics Platform of Integrative Approach with Genomics for Drug Candidate and Metabolite Analysis

Abstract

Micromonospora is the one of prolific sources of bioactive second metabolites (SMs) which are potential drugs due to their efficacy and safety, attributed to their chemical structures. Advances in metabolomics and bioinformatics technologies have significantly increased the number of MS spectrum and genome sequence data that could be used for prediction of potential bioactive SMs. Despite this progress, the rate of discovering novel SMs has declined. Therefore, we developed screening and matching platform between metabolomic and genomic databases to effectively identify new bioactive compounds. We applied the platform to one strain, M. MS-62 which produces antimicrobial effective SM. We analyzed the genome sequence of MS-62 and predicted the potential SMs biosynthetic gene clusters (BGCs) using genome mining tools, such as antiSMASH and PRISM. Tandem mass spectrometry (TMS) was conducted on MS-62 fermented broths varying sampling conditions, matching data to mass spectra databases using GNPS to screen for bioactive candidates. Molecular networking of TMS data helped identify known SM derivatives and link structures to potential BGCs. Finally, we discovered new bioactive SM and its BGC candidate from MS-62. Through this approach, we aim to provide a systematic method for efficiently exploring and analyzing bioactive compounds necessary for the development of new therapeutic drugs.