Back to Search
Start Over
A Cytochrome P450 Catalyzes Oxidative Coupling Formation of Insecticidal Dimeric Indole Piperazine Alkaloids.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 May 27; Vol. 63 (22), pp. e202404000. Date of Electronic Publication: 2024 Apr 12. - Publication Year :
- 2024
-
Abstract
- Cytochrome P450 (CYP450)-catalyzed oxidative coupling is an efficient strategy for using simple building blocks to construct complex structural scaffolds of natural products. Among them, heterodimeric coupling between two different monomers is relatively scarce, and the corresponding CYP450s are largely undiscovered. In this study, we discovered a fungal CYP450 (CpsD) and its associated cps cluster from 37208 CYP450s of Pfam PF00067 family member database and subsequently identified a group of new skeleton indole piperazine alkaloids (campesines A-G) by combination of genome mining and heterologous synthesis. Importantly, CYP450 CpsD mainly catalyzes intermolecular oxidative heterocoupling of two different indole piperazine monomers to generate an unexpected 6/5/6/6/6/6/5/6 eight-ring scaffold through the formation of one C-C bond and two C-N bonds, illuminating its first dimerase role in this family of natural products. The proposed catalytic mechanism of CpsD was deeply investigated by diversified substrate derivatization. Moreover, dimeric campesine G shows good insecticidal activity against the global honeybee pest Galleria mellonella. Our study shows a representative example of discovering new skeleton monomeric and dimeric indole piperazine alkaloids from microbial resources, expands our knowledge of bond formation by CYP450s and supports further development of the newly discovered and engineered campesine family compounds as potential biopesticides.<br /> (© 2024 Wiley-VCH GmbH.)
- Subjects :
- Animals
Biocatalysis
Dimerization
Indole Alkaloids chemistry
Indole Alkaloids metabolism
Molecular Structure
Oxidation-Reduction
Alkaloids chemical synthesis
Alkaloids metabolism
Cytochrome P-450 Enzyme System metabolism
Cytochrome P-450 Enzyme System chemistry
Insecticides chemical synthesis
Insecticides chemistry
Piperazines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 63
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 38527935
- Full Text :
- https://doi.org/10.1002/anie.202404000