Improvement of Antibiotic Productivity by Knock-out of Dauw in Streptomyces Coeruleobidus

Daunorubicin (DNR) is an important anthracycline antibiotic. Its biosynthesis pathway has been well understood, however, the regulation of DNR biosynthesis needs further investigations. An ORF cloned between drrB and dnrX from the genome of a DNR producer, Streptomyces coeruleobidus DM, was named dauW and designated as an orthologous gene with dnrW and drrD. Several plasmids were constructed for over-expression and/or disruption of dauW in DM. Complete disruption of dauW can significantly increase the yield of DNR. We also found that the transcription level of dnrI, a major regulatory protein in the biosynthesis of DNR, and the self-resistance level were improved in dauW knock-out mutant. These results suggested that dauW may be a down-regulatory gene for DNR biosynthesis. Antibiotics productivity in S. coeruleobidus could be improved via regulation of the transcription of dnrI, a SARP regulator. The production of DNR in a high-producer and the yield of epi-DNR in an engineering strain were also increased by disruption of dauW.