Streptomyces genera are a prolific source of secondary metabolites known for the high pharmacological relevance. The multi-enzymatic and highly versatile machinery encoded by NonRibosomal Peptides Synthetases (NRPS) and PolyKetide Synthases (PKS) are responsible to produce near to 50% of antibiotics in pharmaceutical industry.1 The culture extracts from Streptomyces sp. CBMAI 2043 promoted the growth inhibition of Candida albicans pathogen, Bacillus megaterium, Neisseria meningitidis strains, and multiresistant Staphylococcus aureus. Driven by the biochemical tests and the current status of the “Genome to Natural Products” programs we invested in the Whole Genome Shotgun Project of Streptomyces sp. CBMAI 2043, an endophytic strain isolated from Citrus reticulata (tangerine).2 After in silico analysis the metabolic profile of the ethyl acetate extracts from cultivation in several mediums was evaluated by FT-ICR-MS, in both the positive and negative ion modes, using a m/z range between 100 and 2000. The production of some antibiotics entities as desferoxamine E, candicidin, antimycins and a linear peptide by the strain was confirmed as predicted by the genome analysis. Six ion products related to antimycins were identified as the variants A1a, A1b, A12, A19, A8 and A17. Interestingly, the gene cluster responsible to biosynthesize mannopeptimicyns (mpps), a group of glycosylated cyclic hexapeptides (glycopeptides) active against methicillin resistant staphylococci and vancomycin resistance enterococci, was also revealed by genome mining, though under the fermentation conditions we couldn’t identify the production of mpps. In order to associate the mannopeptimycin gene cluster encoded in Streptomyces sp. CBMAI 20143 genome to a possibly produced metabolite we promoted the deletion of the mppB gene involved in the hexapeptide core biosynthesis. The extracts profile from wild type and mppB mutants’ strains were compared and it was not possible to observe a significant change what could infer that the mpp gene cluster in Streptomyces sp. CBMAI 20143 is cryptic. Transcript analysis and heterologous expression of the whole gene cluster using a pESAC-mpp artificial chromosome are now under investigation in order to identify the mannopeptimycin derivative.