Over the past few years, metabolomics has been employed in a broad range of applications in different research fields. Microbial metabolomics has been applied in several microbiological areas, such as identification of microorganisms, cell mutations, functional gene approach, identification of unique metabolic pathways and microbial engineering, leading to a better understanding of the global metabolism and metabolic regulation of certain systems. Metabolites produced by microorganisms constitute a large promising group with diverse applications; however, most of these systems are still unknown and underexplored. In this context, the overall analysis of metabolites involved in a biological system can be used to discover potential biomarkers or specific metabolic changes due to a biological phenomenon studied. In this sense, this review aims to understand the main challenges faced by each step of the workflow in the metabolic analysis of microorganisms and how these difficulties have been overcome. A critical analysis of the articles published within the last five years will be accomplished in this paper to understand how these studies have contributed to the microbial metabolomics research. Moreover, major trends observed in this area will be highlighted here in order to guide readers interested in microbial metabolomics in their future researches.

The fungus Penicillium brasilianum LaBioMMi 136 was isolated as an endophyte from Melia azedarach and has shown to be a prominent producer of great diversity of secondary metabolites, although it does not express some biosynthetic routes to other natural compounds found in Penicillium genera. The present study aimed at the diversification of P. brasilianum secondary metabolism by varying the chemical composition used for its growth. Medium composition supplemented with CuSO4 and MnSO4 locked verruculogen biosynthesis and addressed proline to the production of a series of cyclodepsipeptides identified as JBIR 113, JBIR 114 and JBIR 115, never described for this species so far. The induced cyclodepsipeptide JBIR 113 was isolated by the use of combined chromatographic procedures and identified by spectroscopic methods. The unique structure with three neighboring cyclic amino acids proline and twice pipecolinic acid is rare as natural products and has been described for the first time in terrestrial organism. Verruculogen and JBIR 113 exhibited weak antiparasitary activity against Leishmania amazonensis.