Enhancement of Daptomycin Production by the Method of Combining Ribosome Engineering and Genome Shuffling in Streptomyces roseosporus

摘要

Daptomycin, produced by Streptomyces roseosporus is a novel calcium-dependent cyclic lipopeptide used as antibiotic in treatment of human infections caused by Gram-positive bacteria. However, the yield of daptomycin needs to be further enhanced to reduce the high production cost, which has seriously restricted its clinical application. Here we obtained PRGN21 mutant of S. roseosporus producing the daptomycin with high-yield and having multiple antibiotic resistance to paromomycin, rifampicin, neomycin and gentamicin using the method of combing genome shuffling and ribosome engineering. The daptomycin yield produced by this strain approached 324 mg/L, which was nearly 4-fold higher of that for the parent strain of W2. In period from 48 to 120 h, the dptE transcriptional levels in the PRGN21 mutant of S. roseosporus were significantly enhanced compared to those in S. roseosporus W2 strain, which can explain the ability of PRGN21 mutant to improve the daptomycin biosynthesis.