The acid is then transferred onto an acyl carrier protein (encoded by dptF) and coupled with the N-terminus of the tyrosinase related protein (Trp1) as a fatty acid side-chain ( Wittmann et al., 2008). The daptomycin biosynthesis pathway is initiated by the activation of decanoic acid by DptE (an acyl-CoA ligase). The biosynthetic gene cluster of daptomycin ( dpt) has been identified and includes dptA, dptBC, dptD, dptE, dptF, dptG, dptH, dptI, dptJ, dptP, dptM, and dptN ( Miao et al., 2005).

This CLP is classified as a last-resort antibiotic, along with vancomycin and linezolid ( Gray and Wenzel, 2020), which was first reported by Eli Lilly and Company ( Kirkpatrick et al., 2003) and was approved by the FDA in 2003 to treat skin infections and bacteremia caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) ( Nguyen et al., 2006). Daptomycin is a CLP that is produced by Streptomyces roseosporus through a non-ribosomal peptide synthetase (NRPS) pathway. These results provide guidance for the development and improvement of potential natural products.Ĭyclic lipopeptides (CLPs) are antibiotics widely used for the treatment of infections by Gram-positive organisms ( Gotze et al., 2017), such as rapidly emerging antibiotic-resistant bacteria. RNA-seq also shows Crp to be a multifunctional regulator that modulates primary metabolism and enhances precursor flux to secondary metabolite biosynthesis.

Transcriptome and qPCR analyses showed that some genes related to the daptomycin biosynthetic gene cluster ( dpt) and the pleiotropic regulator ( adpA) were significantly upregulated. We found that daptomycin production from the crp deletion strain decreased drastically, whereas production from the crp overexpression strain increased by 22.1%. In the present study, we demonstrated that the cyclic AMP receptor protein (Crp) plays an important role in producing daptomycin in the S. The biosynthesis of daptomycin is regulated by various factors.

Daptomycin, which is produced by Streptomyces roseosporus, has been characterized as a novel cyclic lipopeptide antibiotic that is effective against Gram-positive bacteria.

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