The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4

Chao, Rebecca R., De Voss, James J. and Bell, Stephen G. (2016) The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4. Rsc Advances, 6 60: 55286-55297. doi:10.1039/c6ra11025h


Author Chao, Rebecca R.
De Voss, James J.
Bell, Stephen G.
Title The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4
Journal name Rsc Advances   Check publisher's open access policy
ISSN 2046-2069
Publication date 2016-06-03
Year available 2016
Sub-type Article (original research)
DOI 10.1039/c6ra11025h
Open Access Status Not Open Access
Volume 6
Issue 60
Start page 55286
End page 55297
Total pages 12
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Collection year 2017
Language eng
Formatted abstract
The cytochrome P450 enzyme, CYP199A4, demethylated 4-methoxybenzoic acid, but not 4-methoxyphenylacetic acid, with high product formation activity. The oxidative demethylation of 3-(4-methoxyphenyl)propionic acid was 8-fold more active than 4-methoxyphenylacetic acid and 4-methoxycinnamic acid was efficiently oxidised at a product formation rate of 180 nmol nmol-P450-1 min-1. Accordingly the oxidation of cinnamic acid derivatives was investigated in order to determine the potential of CYP199A4 to act as a biocatalyst for this important class of biological molecules. 4-Methoxy- and 4-methyl-cinnamic acids bound tightly to CYP199A4 and were better substrates for CYP199A4 than cinnamic acid itself. The oxidations of both 4-methoxy- and 4-methyl-cinnamic acids was 100% selective for attack at the para substituent. Certain dimethoxy substituted cinnamic acids were demethylated more efficiently than 4-methoxycinnamic acid and retained the selectivity for the para-methoxy substituent. Only very low product turnover was observed with 3,5-dimethoxycinnamic acid. 4-Isopropylcinnamic acid was hydroxylated and desaturated by CYP199A4 at the isopropyl group. Cinnamic acids with a para-substituted alkyl- and alkyloxy-cinnamic acid framework were a good fit for the active site of the CYP199A4 enzyme and as a consequence were efficiently and selectively oxidised. Whole-cell oxidations resulted in high yields of product and CYP199A4 could be developed for applications in the biocatalytic oxidation of cinnamic acid derivatives and related phenylpropanoids.
Keyword Heme-dependent cytochrome P450
CYP
4-methoxybenzoic acid
Cinnamic acid
Catalytic oxidation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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