Metabolic pathways and regulatory networks associated to NAI-107 lantibiotic production in Microbispora sp. ATCC-PTA-5024

Giuseppe Gallo, Anna Maria Puglia, Teresa Faddetta, Rosa Alduina, Emilia Palazzotto, Giovanni Renzone

Risultato della ricerca: Otherpeer review

Abstract

The filamentous actinobacterium Microbispora sp. ATCC-PTA-5024produces the lantibiotic NAI-107, which is effective against multidrugresistantGram-positive pathogens. In actinomycetes, the biosynthesisof antibiotics is elicited as a physiological response that is controlledby a complex regulatory network involving general and pathwayspecificregulators. The ‘omics technologies can be useful to exploremolecular physiology in bacterial cells and elucidate molecular andmetabolic events associated to antibiotic production in order to developrobust and economically-feasible production processes. To this aim,differential proteomic analyses, based two-dimensional difference in gelelectrophoresis (2D-DIGE) and mass spectrometry (MS) approaches,combined with differential fluorescence microscopy (DFM) andmolecular genetic studies were carried out on M. sp. ATCC-PTA-5024.M. sp. ATCC-PTA-5024 fermentations, showing a first biomassaccumulation (A) stage followed by a of biomass yield decline (D) stage,revealed that NAI-107 yield starts at mid A stage and increases up to mid D stage. 2D-DIGE and MS analyses were carried out at A and Dstages to reveal patterns of differentially regulated proteins associated toon set and maintenance of NAI-107 production, respectively. Regulatoryand metabolic proteins were identified and possible role in physiologicaldifferentiation of an unknown regulatory protein was investigated bythe construction of an over-expressing strain. Impact of NAI-107 oncell physiology and metabolism was analysed using a non-producingmutant confirming possible role of identified proteins in self-resistancemechanism. Molecular aspect of activation of specific stress responsemechanism were confirmed by DFM.These results originally elucidate regulatory networks, biochemicalpathways and molecular processes occurring during growth andlantibiotic production, thus providing the first functional picture of amember of the Microbispora genus.
Lingua originaleEnglish
Pagine49-
Numero di pagine1
Stato di pubblicazionePublished - 2015

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