Mining of the Catharanthus roseus Genome Leads to Identification of a Biosynthetic Gene Cluster for Fungicidal Sesquiterpenes

Liang, Jincai
An, Tianyue
Zhu, Jian-Xun
Chen, Shan
Zhu, Jian-Hua
Peters, Reuben J.
Yu, Rongmin
Zi, Jiachen
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© 2021 American Chemical Society and American Society of Pharmacognosy
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Biochemistry, Biophysics and Molecular Biology
Characterization of cryptic biosynthetic gene clusters (BGCs) from microbial genomes has been proven to be a powerful approach to discovery of new natural products. However, such a genome mining approach to discovery of bioactive plant metabolites has been muted. The plant BGCs characterized to date encode pathways for antibiotics important in plant defense against microbial pathogens, providing a means to discover such phytoalexins by mining plant genomes. Here is reported discovery and characterization of a minimal BGC from the medicinal plant Catharanthus roseus, consisting of an adjacent pair of genes encoding a terpene synthase (CrTPS18) and cytochrome P450 (CYP71D349). These two enzymes act sequentially, with CrTPS18 acting as a sesquiterpene synthase, producing 5-epi-jinkoh-eremol (1), which CYP71D349 further hydroxylates to debneyol (2). Infection studies with maize revealed that 1 and 2 exhibit more potent fungicidal activity than validamycin. Accordingly, this study demonstrates that characterization of such cryptic plant BGCs is a promising strategy for discovery of potential agrochemical leads. Moreover, despite the observed absence of 1 and 2 in C. roseus the observed transcriptional regulation is consistent with their differential fungicidal activity, suggesting that such conditional co-expression may be sufficient to drive BGC assembly in plants.
This is a manuscript of an article published as Liang, Jincai, Tianyue An, Jian-Xun Zhu, Shan Chen, Jian-Hua Zhu, Reuben J. Peters, Rongmin Yu, and Jiachen Zi. "Mining of the Catharanthus roseus Genome Leads to Identification of a Biosynthetic Gene Cluster for Fungicidal Sesquiterpenes." Journal of Natural Products 84, no. 10 (2021): 2709-2716. doi:10.1021/acs.jnatprod.1c00588. Posted with permission.