Metabolic Pathways in Microbispora sp. ATCC-PTA 5024, Producer of NAI-107 Lantibiotic

The actinomycete Microbispora sp. ATCC-PTA-5024 produces the lantibiotic NAI-107 (1) a promising drug to treat multidrug-resistant pathogen infections (2). Microbispora is a poorly characterized and this limited knowledge is detrimental to set-up NAI-107 production processes to efficiently deliver high-quality compound. High throughput techniques, like proteomics, may give insights on strain molecular physiology and biochemical capability and, above all, on metabolic pathways and regulatory mechanisms thereof associated with antibiotic production (3). Thus Microbispora differential proteomic analyses were comparatively carried-out on wild type, null and super-producer strains by mean of 2-D-Differential Gel Electrophoresis and mass spectrometry procedures. This study revealed differential regulation of pleiotropic regulators, stress response factors and proteins involved in many cell processes and metabolic pathways associated with NAI-107 production on-set and maintenance. In particular, proteins involved in molecular processes like amino sugar, nitrogen, phosphate and sulphur metabolism, oxidative stress and antibiotic biosynthesis and resistance are positively correlated while proteins involved in glycolysis, amino acid and nucleotide metabolism are negatively associated to NAI- 107. Therefore, these data coupled to gene ontology, revealed a comprehensive set of differentially regulated proteins which may play roles as trigger or sustaining or response factors in NAI-107 production. Altogether this information may be used as a knowledge background to rationally improve NAI-107 production by Microbispora fermentation optimization or for strain improvement by genetic engineering on targeted genes.