Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in Streptomyces.
Metab Eng
; 48: 254-268, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29944936
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Streptomyces
/
Proteínas de Bactérias
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Proteínas de Ligação ao Ferro
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Engenharia Metabólica
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Metab Eng
Assunto da revista:
ENGENHARIA BIOMEDICA
/
METABOLISMO
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália