| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| Outline of Final Research Achievements |
Teleocidin B is a cyclic peptidic terpenoids characterized with 9-membered ring indolactam structure and a potent protein kinase C activator. In this study, we report the mechanistic characterization of indolactam-forming P450 enzymes TleB and its homolog HinD. Interestingly, the TleB and HinD accepted the various dipeptide substrates, and generated not only indolactam analogs but also unusual 6/5/6 ring structures in vitro. Comparisons of the complex crystal structures with different substrates revealed the important residues and possible binding modes in the active site. Combination of the findings from the enzyme assays and X-ray crystal structures of TleB and HinD, we proposed a mechanism of the enzyme catalyzed intramolecular C(sp2)-H bonds amination. We also identified the reaction of HinD homologs from Streptoalloteichus hindustanus.
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