Abstract
Lobophorins A (1) and B (2) belong to a large group of spirotetronate natural products with potent antibacterial and antitumor activities. The cloning of the lobophorin biosynthesis gene cluster from the deep-sea-derived Streptomyces sp. SCSIO 01127 identified a sugar-O-methyltransferase-encoding gene lobS1. The lobS1 inactivation mutant accumulated two new lobophorin analogs 3 and 4, different from 1 and 2 by lacking the 4-methyl group at the terminal l-digitoxose, respectively. Biochemical experiments verified that LobS1 was a SAM-dependent sugar-O-methyltransferase that required divalent metal ions for better activity. Antibacterial assays revealed compounds 3 and 4 were generally less potent than compounds 1 and 2. These findings suggest that the methylation on the terminal digitoxose by LobS1 tailors lobophorin biosynthesis and highlights the importance of this methylation for antibacterial potence.
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Acknowledgments
This work is supported in part by grants from the National Science Foundation of China (31125001), the Funds of the Chinese Academy of Sciences for Key Topics in Innovation Engineering (KZCX2-YW-JC202, KSCX2-EW-G-12), and the funds from Ministry of Science and Technology of China (2010CB833805 and 2012AA092104). C. Z. is a scholar of the “100 Talents Project” of Chinese Academy of Sciences (08SL111002). We are grateful to the analytical facility of South China Sea Institute of Oceanology for recording NMR data.
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**ao, J., Zhang, Q., Zhu, Y. et al. Characterization of the sugar-O-methyltransferase LobS1 in lobophorin biosynthesis. Appl Microbiol Biotechnol 97, 9043–9053 (2013). https://doi.org/10.1007/s00253-013-5083-7
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DOI: https://doi.org/10.1007/s00253-013-5083-7