AI Article Synopsis
- Dimeric natural products, like (−)-ditryptophenaline from Aspergillus flavus, show promise for biological activities, such as inhibiting pain and inflammation by targeting the substance P receptor.
- By using gene knockout techniques and yeast gene expression, researchers identified the gene cluster responsible for the biosynthesis of this specific dimeric compound for the first time.
- The cytochrome P450 enzyme DtpC plays a crucial role in both forming a key ring structure and facilitating the dimerization process, with the ability to create new compounds from different precursors, suggesting a radical-mediated dimerization mechanism.
Article Abstract
As dimeric natural products frequently exhibit useful biological activities, identifying and understanding their mechanisms of dimerization is of great interest. One such compound is (−)-ditryptophenaline, isolated from Aspergillus flavus, which inhibits substance P receptor for potential analgesic and anti-inflammatory activity. Through targeted gene knockout in A. flavus and heterologous yeast gene expression, we determined for the first time the gene cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid. We also determined that a single cytochrome P450, DtpC, is responsible not only for pyrroloindole ring formation but also for concurrent dimerization of N-methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the formation of two new dimeric compounds from a non-native monomeric precursor, brevianamide F. A radical-mediated mechanism of dimerization is proposed.
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| http://dx.doi.org/10.1002/cbic.201300751 | DOI Listing |
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