Síntesis de antibioticos en streptomyces y su relación con el metabolismo global

Résumé

Apart from oleandomycin and oviedomycin, Streptomyces antibioticus has a biosynthetic cluster that codes for an unidentified polyketide derived from the condensation of acetyl-CoA. In addition to the structural genes needed for the synthesis of the compound, this cluster contains a pathway specific regulator (orfI). In addition, the cluster contains a two component system (ORFD1/ORFD2) which specifically induces orfI transcription. In this work, by using footprint analysis we¿ve elucidated the target sequence recognized by ORFD1 within the promoter sequence of orfI. This regulatory mechanism has been used under heterologous conditions as a model system to study the regulatory process that leads to antibiotic biosynthesis in Streptomyces coelicolor. For such purposes, genomic analysis has been conducted in the resulting strains. The studies undertaken led to the following conclusions: (a) the synthesis of the polyketide antibiotic actinorhodin goes together with an increase in the transcription rates of its pathway specific regulator: actII-ORF4; (b) there is a correlation between the synthesis of actinorhodin and the activation of the genes involved in the oxidative stress response. The search for genes in S. coelicolor that are similar to orfD1/orfD2 two component system in S. antibioticus, resulted in the characterization of the SCO2307/SCO2308 two component system. This proteins work as a possible regulator for the synthesis of actinorhodin, CDA, tha chaplins, the rodlins y the nitrogen metabolism.