Regulatory and metabolic proteins differentially expressed during NAI-107 production in Microbispora sp. ATCC-PTA 5024

Microbispora sp. ATCC-PTA-5024, the producer of lantibiotic NAI-107, is a poorly characterized actinomycete. High throughput techniques, like proteomics, may give insights on strain molecular physiology and biochemical capability and, above all, on metabolic pathways and regulatory mechanisms associated with antibiotic production. 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 reveals differential regulation of proteins involved in many cell processes and metabolic pathways associated with NAI-107 production on-set and maintenance. In particular, gene ontology clusterization shows that during NAI-107 production proteins involved in amino sugar, nitrogen, phosphate and sulphur metabolism, oxidative stress and antibiotic biosynthesis and resistance are up-regulated while proteins involved in glycolysis, amino acid and nucleotide metabolism are downregulated. Thus, these data reveal a comprehensive set of differentially regulated proteins which may play a key role in NAI-107 production. Altogether this information may be used to rationally improve NAI- 107 production by Microbispora fermentation optimization or by strain improvement by genetic engineering of targeted genes.