The cyclization of sedoheptulose 7-phosphate to 2-epi-5-epi-valiolone, catalyzed by the 2-epi-5-epi-valiolone synthases, is the first committed step in the biosynthesis of C7N-aminocyclitol-containing natural products, such as validamycin and acarbose. These natural products contain in their structures a valienamine unit, which is important for their biological activity. The same core unit is also found in salbostatin, a related pseudodisaccharide that has strong trehalase inhibitory activity. In silico analysis of the putative biosynthetic gene cluster of salbostatin from Streptomyces albus ATCC 21838 revealed 20 open reading frames, including an acbC homolog gene (salQ), which is believed to be involved in the biosynthesis of salbostatin. The salQ gene was overexpressed in Escherichia coli and the catalytic function of the recombinant protein was confirmed to be a 2-epi-5-epi-valiolone synthase. In addition, SalF, SalL, SalM, SalN, SalO, and SalR were found to be homologous to AcbR, AcbM, AcbL, AcbN, AcbO, and AcbP from the acarbose pathway, respectively, which suggests that the biosynthesis of C7N-aminocyclitol moiety of salbostatin may be very similar to that of acarbose.
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The authors thank Patricia M. Flatt for critical reading of the manuscript. This research was supported by the Driving Force Project for the Next Generation, Gyeonggi Provincial Government, Republic of Korea and general research funds from the College of Pharmacy Oregon State University.
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Choi, W.S., Wu, X., Choeng, Y. et al. Genetic organization of the putative salbostatin biosynthetic gene cluster including the 2-epi-5-epi-valiolone synthase gene in Streptomyces albus ATCC 21838. Appl Microbiol Biotechnol 80, 637–645 (2008). https://doi.org/10.1007/s00253-008-1591-2
- 2-epi-5-epi-valiolone synthase
- Streptomyces albus