Improvement of daptomycin yield by overexpression of the accessory genes of daptomycin gene cluster

摘要

The effects of the accessory genes flanking the non-ribosomal peptide synthetase (NRPS) genes on daptomycin production were investigated by overexpression under the control of?ermE*?promoter via the integrative?Escherichia coli–Streptomycesvector pIB139. The yield of daptomycin was promoted significantly when either of the upstream accessory genes of?dptE?and?dptF?or downstream accessory genes ofdptG,?dptH,?dptI?and?dptJ?was overexpressed individually or by a combined manner. The yield of daptomycin further increased to 869 ± 25 mg/L, approximately 42.6% higher than the parental strain of LC-54-16, when all of the six upstream and downstream accessory genes were overexpressed simultaneously. The results above suggested that the upstream and downstream accessory genes of NRPS had positive cooperativity in the biosynthesis of daptomycin. The transcriptional levels of both the upstream and the downstream accessory genes of NRPS in HP-EJ were approximately 2.5-fold as high as that in the parental strain of LC-54-16.