| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2008: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
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| Research Abstract |
Non-ribosomal peptide synthetase (NRPS) promotes condensations of amino acids forming amide linkages, with some modifications. We found that a single NRPS SfmC of the potent antitumor agents saframycin catalyzes a seven-step transformation from readily synthesized dipeptidyl substrates with long acyl chains into a pentacyclic tetrahydroisoquinoline scaffold. Based on deletion mutant analyses, we proposed the detailed mechanism involving the reductions of various peptidyl thioesters by an identical R-domain followed by the C-domain-mediated Pictet-Spengler reactions in an iterative manner.
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