Engineering cytochrome P450 enzyme systems for biomedical and biotechnological applications.

cytochrome P450 directed evolution electron source engineering enzyme mechanism ferredoxin light activation metabolic engineering protein engineering redox partner proteins substrate engineering substrate specificity

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
17 01 2020
Historique:
pubmed: 8 12 2019
medline: 4 9 2020
entrez: 8 12 2019
Statut: ppublish

Résumé

Cytochrome P450 enzymes (P450s) are broadly distributed among living organisms and play crucial roles in natural product biosynthesis, degradation of xenobiotics, steroid biosynthesis, and drug metabolism. P450s are considered as the most versatile biocatalysts in nature because of the vast variety of substrate structures and the types of reactions they catalyze. In particular, P450s can catalyze regio- and stereoselective oxidations of nonactivated C-H bonds in complex organic molecules under mild conditions, making P450s useful biocatalysts in the production of commodity pharmaceuticals, fine or bulk chemicals, bioremediation agents, flavors, and fragrances. Major efforts have been made in engineering improved P450 systems that overcome the inherent limitations of the native enzymes. In this review, we focus on recent progress of different strategies, including protein engineering, redox-partner engineering, substrate engineering, electron source engineering, and P450-mediated metabolic engineering, in efforts to more efficiently produce pharmaceuticals and other chemicals. We also discuss future opportunities for engineering and applications of the P450 systems.

Identifiants

pubmed: 31811088
pii: S0021-9258(17)49939-X
doi: 10.1074/jbc.REV119.008758
pmc: PMC6970918
doi:

Substances chimiques

Steroids 0
Xenobiotics 0
Cytochrome P-450 Enzyme System 9035-51-2

Banques de données

PDB
['1OXA', '2JJN', '6B11', '1JPZ', '2X7Y', '3A4G', '2ZBX', '2ZBZ', '4OQR', '2C6H', '2C7X', '5UHU', '1OG2', '6DA2', '3N9Y', '3RUK', '4YT3', '1DT6']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

833-849

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM118122
Pays : United States

Informations de copyright

© 2020 Li et al.

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Auteurs

Zhong Li (Z)

Shandong Provincial Key Laboratory of Synthetic Biology and CAS Key Laboratory of Biofuels at Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101, China.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.
University of Chinese Academy of Sciences, Beijing 100049, China.

Yuanyuan Jiang (Y)

Shandong Provincial Key Laboratory of Synthetic Biology and CAS Key Laboratory of Biofuels at Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101, China.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.
University of Chinese Academy of Sciences, Beijing 100049, China.

F Peter Guengerich (FP)

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.

Li Ma (L)

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

Shengying Li (S)

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237 Shandong, China.

Wei Zhang (W)

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China zhang_wei@sdu.edu.cn.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237 Shandong, China.

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