High Resolution-Mass Spectrometry as a unique Bioanalytical Tool in Natural Product Studies

a gorgeous font of chemical compounds for drug discovery. Advances in genome sequencing and mining, in addition to bio-synthetic pathway manipulation, allow the expression of silent (cryptic) gene clusters and provide the access to previously underexplored sources such as new groups of microorganisms, consequently highlighting that is possible to discover new chemical entities. A fundamental role is played by the progress in compound detection technologies. Indeed, the main intent is to shorten the time necessary to discard known compounds and identify the new ones. High resolution mass spectrometry (HRMS) has become a reliable detection responding to several analytical challenges. Actually, the employment of Mass Spectrometry has grown up like a giant tree developing many branches and a thick crown that invaded almost all research fields regarding the omics sciences (metabolomics, proteomics, lipidomics, etc.) [1]. Hence, an extraordinary time started to strongly stimulate analytical data acquisition; it became possible to directly analyze crude extracts without the need for purification/ isolation of specific species and large data sets can be processed at once [2]. Several experimental databases, such as Dictionary of Natural Products DNP, ChemSpider, REAXYS, and several software tools such as METLIN, MIDAS and MetFRAg [3] can be used for metabolite identification in metabolomics; molecular structures were provided and matching of measured mass spectra (MS/MS) against the predicted fragments of metabolites can be performed although very often the signals found do not correspond with the described ones [4]. MS based metabolomics became the technique of choice for rapid detection and dereplication of secondary metabolites, not only in natural product microbial cultures. Clear indications for performing this study are available [5] but software tailored to predict all the metabolites modifications have not yet been fully developed, established that not only enzymatic transformations but also exogenous compounds from different environmental factors can contribute to production of new metabolites. We would like to comment some of advantages and challenges of HRMS and its future potential leading to interesting structural information that can direct the an1Fondazione Istituto Insubrico Ricerca per la Vita, 21040 Gerenzano (Va), Italy 2Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, 20133 Milan, Italy