Shanghai Institute of Pharmaceutical Industry, State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai 200437, China.
Microbiol Res. 2011 Oct 20;166(7):539-47. doi: 10.1016/j.micres.2010.10.006. Epub 2011 Jan 15.
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.
柔红霉素（DNR）是一种重要的蒽环类抗生素。其生物合成途径已经得到很好的理解，然而，DNR 生物合成的调控需要进一步研究。从 DNR 产生菌天蓝链霉菌 DM 的基因组中克隆的 drrB 和 dnrX 之间的一个 ORF 被命名为 dauW，并被指定为 dnrW 和 drrD 的同源基因。构建了几个质粒用于在 DM 中过表达和/或敲除 dauW。dauW 的完全敲除可显著提高 DNR 的产量。我们还发现，DNR 生物合成的主要调节蛋白 dnrI 的转录水平和自身抗性水平在 dauW 敲除突变体中得到了提高。这些结果表明，dauW 可能是 DNR 生物合成的下调基因。通过调节 SARP 调节因子 dnrI 的转录，可以提高天蓝链霉菌的抗生素产量。通过敲除 dauW，高产菌中 DNR 的产量和工程菌中表柔红霉素的产量也得到了提高。
