Cytochrome P450: Taming a wild type enzyme

Sang Taek Jung; Ryan Lauchli; Frances H. Arnold

doi:10.1016/j.copbio.2011.02.008

Cytochrome P450: Taming a wild type enzyme

Sang Taek Jung, Ryan Lauchli, Frances H. Arnold

Research output: Contribution to journal › Review article › peer-review

225 Citations (Scopus)

Abstract

Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable' - they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities. Their ability to adapt to new challenges upon mutation may reflect the nonpolar nature of their active sites as well as their high degree of conformational variability.

Original language	English
Pages (from-to)	809-817
Number of pages	9
Journal	Current Opinion in Biotechnology
Volume	22
Issue number	6
DOIs	https://doi.org/10.1016/j.copbio.2011.02.008
Publication status	Published - 2011 Dec
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Biomedical Engineering

Access to Document

10.1016/j.copbio.2011.02.008

Cite this

@article{62e56d6efaaa4fb88a888d4b6bb5ba5f,

title = "Cytochrome P450: Taming a wild type enzyme",

abstract = "Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable' - they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities. Their ability to adapt to new challenges upon mutation may reflect the nonpolar nature of their active sites as well as their high degree of conformational variability.",

author = "Jung, {Sang Taek} and Ryan Lauchli and Arnold, {Frances H.}",

note = "Funding Information: The authors acknowledge the support of the U.S. Department of Energy , BES grant DE-FG02-06ER15762 , National Institutes of Health ARRA grant 2R01GM068664-05A1, and National Institutes of Health grant 1R01-DA028299 . RL acknowledges the support of NIH fellowship 1F32GM095061-01 . The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies. We thank Eric Brustad, Philip Romero, Kersten Rabe, Mike Chen, and Indira Wu for helpful comments on various drafts of this review. ",

year = "2011",

month = dec,

doi = "10.1016/j.copbio.2011.02.008",

language = "English",

volume = "22",

pages = "809--817",

journal = "Current Opinion in Biotechnology",

issn = "0958-1669",

publisher = "Elsevier Limited",

number = "6",

}

TY - JOUR

T1 - Cytochrome P450

T2 - Taming a wild type enzyme

AU - Jung, Sang Taek

AU - Lauchli, Ryan

AU - Arnold, Frances H.

N1 - Funding Information: The authors acknowledge the support of the U.S. Department of Energy , BES grant DE-FG02-06ER15762 , National Institutes of Health ARRA grant 2R01GM068664-05A1, and National Institutes of Health grant 1R01-DA028299 . RL acknowledges the support of NIH fellowship 1F32GM095061-01 . The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies. We thank Eric Brustad, Philip Romero, Kersten Rabe, Mike Chen, and Indira Wu for helpful comments on various drafts of this review.

PY - 2011/12

Y1 - 2011/12

N2 - Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable' - they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities. Their ability to adapt to new challenges upon mutation may reflect the nonpolar nature of their active sites as well as their high degree of conformational variability.

AB - Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable' - they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities. Their ability to adapt to new challenges upon mutation may reflect the nonpolar nature of their active sites as well as their high degree of conformational variability.

UR - http://www.scopus.com/inward/record.url?scp=82755189689&partnerID=8YFLogxK

U2 - 10.1016/j.copbio.2011.02.008

DO - 10.1016/j.copbio.2011.02.008

M3 - Review article

C2 - 21411308

AN - SCOPUS:82755189689

SN - 0958-1669

VL - 22

SP - 809

EP - 817

JO - Current Opinion in Biotechnology

JF - Current Opinion in Biotechnology

IS - 6

ER -

Cytochrome P450: Taming a wild type enzyme

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this