Journal article
Benign Synthesis of 2-Ethylhexanoic Acid by Cytochrome P450cam: Enzymatic, Crystallographic, and Theoretical Studies
Biochemistry (Easton), Vol.40(32), pp.9532-9538
08/14/2001
Handle:
https://hdl.handle.net/2376/103582
PMID: 11583152
Abstract
This study examines the ability of P450cam to catalyze the formation of 2-ethylhexanoic acid from 2-ethylhexanol relative to its activity on the natural substrate camphor. As is the case for camphor, the P450cam exhibits stereoselectivity for binding (R)- and (S)-2-ethylhexanol. Kinetic studies indicate (R)-2-ethylhexanoic acid is produced 3.5 times as fast as the (S)-enantiomer. In a racemic mixture of 2-ethylhexanol, P450cam produces 50% more (R)-2-ethylhexanoic acid than (S)-2-ethylhexanoic acid. The reason for stereoselective 2-ethylhexanoic acid production is seen in regioselectivity assays, where (R)-2-ethylhexanoic acid comprises 50% of total products while (S)-2-ethylhexanoic acid comprises only 13%. (R)- and (S)-2-ethylhexanol exhibit similar characteristics with respect to the amount of oxygen and reducing equivalents consumed, however, with (S)-2-ethylhexanol turnover producing more water than the (R)-enantiomer. Crystallographic studies of P450cam with (R)- or (S)-2-ethylhexanoic acid suggest that the (R)-enantiomer binds in a more ordered state. These results indicate that wild-type P450cam displays stereoselectivity toward 2-ethylhexanoic acid synthesis, providing a platform for rational active site design.
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Details
- Title
- Benign Synthesis of 2-Ethylhexanoic Acid by Cytochrome P450cam: Enzymatic, Crystallographic, and Theoretical Studies
- Creators
- Kevin J FrenchMichael D StricklerDan A RockDenise A RockGrace A BennettJan L WahlstromBarry M GoldsteinJeffrey P Jones
- Publication Details
- Biochemistry (Easton), Vol.40(32), pp.9532-9538
- Academic Unit
- Chemistry, Department of
- Publisher
- American Chemical Society
- Identifiers
- 99900546800701842
- Language
- English
- Resource Type
- Journal article