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Issue 60, 2016, Issue in Progress
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The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4

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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.

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

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The article was received on 28 Apr 2016, accepted on 02 Jun 2016 and first published on 03 Jun 2016


Article type: Paper
DOI: 10.1039/C6RA11025H
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RSC Adv., 2016,6, 55286-55297

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

    R. R. Chao, J. J. De Voss and S. G. Bell, RSC Adv., 2016, 6, 55286
    DOI: 10.1039/C6RA11025H

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