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The standalone aminopeptidase PepN catalyzes the maturation of blasticidin S from leucylblasticidin S

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  • The peptidyl nucleoside blasticidin S (BS) isolated from Streptomyces griseochromogenes was the first non-mercurial fungicide used on a large scale to prevent rice blast. In the biosynthesis of BS, leucylblasticidin S (LBS) was suggested as the penultimate metabolite with 20-fold less inhibitory activity than the final product BS. Incomplete conversion of LBS to BS at a variable efficiency ranging from 10% to 90% was observed either in the native strain S. griseochromogenes or a heterologous producer Streptomyces lividans WJ2. In this study, we determined that maturation of BS from LBS is not a spontaneous process but is governed by a standalone peptidase PepN, which hydrolyzes LBS in a pH-sensitive way with most appropriate of pH 7~8 but is inactive when the pH is below 5 or above 10. PepN1 and PepN2, two neighboring PepN homologs from Streptomyces lividans were purified in E. coli but displayed ca.100-fold difference in LBS hydrolytic activity. Overexpression of pepN1 in WJ2 enhanced BS yield by 100% and lowered the ratio of LBS to BS from 2:1 to 2:3. This work presents the expansion of the biological role for PepN in antibiotic maturation and the first report of hydrolysis of beta amide linkage by this conserved enzyme.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/articles/srep17641
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  • Yu, G., Li, L., Liu, X., Liu, G., Deng, Z., Zabriskie, M. T., ... & He, X. (2015). The standalone aminopeptidase PepN catalyzes the maturation of blasticidin S from leucylblasticidin S. Scientific Reports, 5, 17641. doi:10.1038/srep17641
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  • 5
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  • This work received support from the National Natural Science Foundation of China (31470195), 973 program from the Ministry of Science and Technology (2012CB721004).
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