Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in Streptomyces

Giuseppe Gallo, Anna Maria Puglia, Alberto Sutera, Clelia Peano, Pietro Alifano, Daniela Rizzo, Eva Pinatel, Daniela Fico, Giuseppe Egidio De Benedetto, Mariangela Testini, Matteo Calcagnile, Adelfia Talà, Luisa Siculella, Fabrizio Damiano, Gianluca De Bellis, Andrea Scaloni, Giovanni Renzone

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6 Citazioni (Scopus)

Abstract

Pirins are evolutionarily conserved iron-containing proteins that are found in all kingdoms of life, and have been implicated in diverse molecular processes, mostly associated with cellular stress. In the present study, we started from the evidence that the insertional inactivation of pirin-like gene SAM23877_RS18305 (pirA) by ΦC31 Att/Int system-based vectors in spiramycin-producing strain Streptomyces ambofaciens ATCC 23877 resulted in marked effects on central carbon and energy metabolism gene expression, high sensitivity to oxidative injury and repression of polyketide antibiotic production. By using integrated transcriptomic, proteomic and metabolite profiling, together with genetic complementation, we here show that most of these effects could be traced to the inability of the pirA-defective strain to modulate beta-oxidation pathway, leading to an unbalanced supply of precursor monomers for polyketide biosynthesis. Indeed, in silico protein-protein interaction modeling and in vitro experimental validation allowed us to demonstrate that PirA is a novel redox-sensitive negative modulator of very long-chain acyl-CoA dehydrogenase, which catalyzes the first committed step of the beta-oxidation pathway.
Lingua originaleEnglish
pagine (da-a)254-268
Numero di pagine15
RivistaMetabolic Engineering
Volume48
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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    Gallo, G., Puglia, A. M., Sutera, A., Peano, C., Alifano, P., Rizzo, D., Pinatel, E., Fico, D., De Benedetto, G. E., Testini, M., Calcagnile, M., Talà, A., Siculella, L., Damiano, F., De Bellis, G., Scaloni, A., & Renzone, G. (2018). Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in Streptomyces. Metabolic Engineering, 48, 254-268.