» Articles » PMID: 31423290

P450 Monooxygenases Enable Rapid Late-Stage Diversification of Natural Products C-H Bond Activation

Overview
Journal ChemCatChem
Date 2019 Aug 20
PMID 31423290
Citations 30
Authors
Affiliations
Soon will be listed here.
Abstract

The biological potency of natural products has been exploited for decades. Their inherent structural complexity and natural diversity might hold the key to efficiently address the urgent need for the development of novel pharmaceuticals. At the same time, it is that very complexity, which impedes necessary chemical modifications such as structural diversification, to improve the effectiveness of the drug. For this purpose, Cytochrome P450 enzymes, which possess unique abilities to activate inert sp-hybridised C-H bonds in a late-stage fashion, offer an attractive synthetic tool. In this review the potential of cytochrome P450 enzymes in chemoenzymatic lead diversification is illustrated discussing studies reporting late-stage functionalisations of natural products and other high-value compounds. These enzymes were proven to extend the synthetic toolbox significantly by adding to the flexibility and efficacy of synthetic strategies of natural product chemists, and scientists of other related disciplines.

Citing Articles

Enzymkatalysierte späte Modifizierungen: Besser spät als nie.

Romero E, Jones B, Hogg B, Rue Casamajo A, Hayes M, Flitsch S Angew Chem Weinheim Bergstr Ger. 2024; 133(31):16962-16993.

PMID: 38505660 PMC: 10946893. DOI: 10.1002/ange.202014931.


The Impact of Metagenomics on Biocatalysis.

Hogg B, Schnepel C, Finnigan J, Charnock S, Hayes M, Turner N Angew Chem Int Ed Engl. 2024; 63(21):e202402316.

PMID: 38494442 PMC: 11497237. DOI: 10.1002/anie.202402316.


Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing.

Huo T, Zhao X, Cheng Z, Wei J, Zhu M, Dou X Acta Pharm Sin B. 2024; 14(3):1030-1076.

PMID: 38487004 PMC: 10935128. DOI: 10.1016/j.apsb.2023.11.021.


Predictive Minisci late stage functionalization with transfer learning.

King-Smith E, Faber F, Reilly U, Sinitskiy A, Yang Q, Liu B Nat Commun. 2024; 15(1):426.

PMID: 38225239 PMC: 10789750. DOI: 10.1038/s41467-023-42145-1.


Convergence in determining enzyme functional descriptors across Kemp eliminase variants.

Jiang Y, Stull S, Shao Q, Yang Z Electron Struct. 2023; 4(4).

PMID: 37425623 PMC: 10327861. DOI: 10.1088/2516-1075/acad51.


References
1.
de Souza R, Miranda L, Bornscheuer U . A Retrosynthesis Approach for Biocatalysis in Organic Synthesis. Chemistry. 2017; 23(50):12040-12063. DOI: 10.1002/chem.201702235. View

2.
Firn R, Jones C . Natural products--a simple model to explain chemical diversity. Nat Prod Rep. 2003; 20(4):382-91. DOI: 10.1039/b208815k. View

3.
Shugrue C, Miller S . Applications of Nonenzymatic Catalysts to the Alteration of Natural Products. Chem Rev. 2017; 117(18):11894-11951. PMC: 5742423. DOI: 10.1021/acs.chemrev.7b00022. View

4.
Patridge E, Gareiss P, Kinch M, Hoyer D . An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today. 2015; 21(2):204-7. DOI: 10.1016/j.drudis.2015.01.009. View

5.
Yu X, Sun D . Macrocyclic drugs and synthetic methodologies toward macrocycles. Molecules. 2013; 18(6):6230-68. PMC: 4374646. DOI: 10.3390/molecules18066230. View