Abstract
Ramoplanins are lipopeptides effective against a wide range of Gram-positive pathogens. Ramoplanin A2 is in Phase III clinical trials. The structure–activity relationship of the unique 2Z,4E-fatty acid side-chain of ramoplanins indicates a significant contribution to the antimicrobial activities but ramoplanin derivatives with longer 2Z,4E-fatty acid side-chains are not easy to obtain by semi-synthetic approaches. To construct a strain that produces such analogues, an acyl-CoA ligase gene in a ramoplanin-producing Actinoplanes was inactivated and a heterologous gene from an enduracidin producer (Streptomyces fungicidicus) was introduced into the mutant. The resulting strain produced three ramoplanin analogues with longer alkyl chains, in which X1 was purified. The MIC value of X1 was ~0.12 μg/ml against Entrococcus sp. and was also active against vancomycin-resistant Staphylococcus aureus (MIC = 2 μg/ml).
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (81072557, 81172962, and 81202442), the Science and Technology Commission of Shanghai Municipality (11QB1406300) and the Ministry of Science and Technology of China (Grant No. 2009ZX09301-007).
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Pan, HX., Chen, ZZ., Shao, L. et al. Production of ramoplanin analogues by genetic engineering of Actinoplanes sp.. Biotechnol Lett 35, 1685–1692 (2013). https://doi.org/10.1007/s10529-013-1261-z
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DOI: https://doi.org/10.1007/s10529-013-1261-z