Issue 18, 2019

Electricity-driven 7α-hydroxylation of a steroid catalyzed by a cytochrome P450 monooxygenase in engineered yeast

Abstract

NAD(P)H are the cofactors of the cytochrome P450 monooxygenases for the catalytic hydroxylation of steroids, which is notoriously challenging for traditional synthetic chemistry due to the requirement of specificity and chirality. However, an undersupply of NAD(P)H is a crucial bottleneck in restricting the conversion rate of P450-catalyzed steroid hydroxylation. To address the problem of cofactor undersupply and enhance the biotransformation from dehydroepiandrosterone (DHEA) to 7α-OH-DHEA, an electricity-driven NAD(P)H regeneration shortcut was incorporated into recombinant Saccharomyces cerevisiae harbouring 7α-hydroxylase (CYP7B1) to construct a P450 bioelectrocatalytic system (BES). The BES could collaboratively utilize electrons derived from both electrodes and the oxidation of carbon sources, enabling intracellular NAD(P)H regeneration via the concomitant electron shuttle (i.e., neutral red (NR))-mediated extracellular electron transfer (EET) pathway and the oxidation of glucose to facilitate the P450 enzyme-catalysed hydroxylation of steroids. Thus, the 7α-OH-DHEA yield reached 288.6 ± 7.8 mg L−1 in the BES, ∼2.4-fold its counterpart in the absence of EET (122.1 ± 3.7 mg L−1). For the first time, a NR-mediated BES was exhibited to be an efficient strategy to enhance steroid hydroxylation in engineered yeast, being promising for steroid conversion in pharmaceutical engineering.

Graphical abstract: Electricity-driven 7α-hydroxylation of a steroid catalyzed by a cytochrome P450 monooxygenase in engineered yeast

Supplementary files

Article information

Article type
Paper
Submitted
29 jún. 2019
Accepted
13 ágú. 2019
First published
13 ágú. 2019

Catal. Sci. Technol., 2019,9, 4877-4887

Electricity-driven 7α-hydroxylation of a steroid catalyzed by a cytochrome P450 monooxygenase in engineered yeast

Z. Zhang, F. Li, Y. Cao, Y. Tian, J. Li, Y. Zong and H. Song, Catal. Sci. Technol., 2019, 9, 4877 DOI: 10.1039/C9CY01288E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements