Multi-omics analysis of mutagenized S. rimosus reveals synergistic changes that drive oxytetracycline production towards industrial efficiency and opens a new route to heterologous polyketides

The present work provides a multi-omics systems-wide view on S. rimosus. Using genomics, transcriptomics, proteomics, and metabolomics, we compared the wild type with an OTC-overproducing derivative, previously obtained by classical mutagenesis. The integration of the data provided a deep insight into the underlying metabolic and regulatory networks that mediate high-level OTC formation. Strikingly, the overproducer revealed a synergistically activated supply of acetyl-CoA and malonyl CoA and increased abundance of various CoA thioesters. Comparison of the transcriptomes of two mutant strains, a hyperproducer derived from the wildtype by chemical mutagenesis and a null mutant derived from the hyperproducer by tergeted deletion of the OTC production cluster, against the wildtype strain. All cells were grown for 24h in liquid medium, all experiments were performed in triplicate