Cyclic Deracemization of Secondary Benzylic Alcohols via Simultaneous Photocatalysis and Whole-cell Biocatalysis

05 June 2025, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Photobiocatalysis enables remarkable synthetic transformations by combining the exquisite stereoselectivity of enzymes with the mild generation of high-energy intermediates by photocatalysis, but practical applications remain limited due to enzyme photodamage. The deracemization of secondary alcohols is a key model reaction for photobiocatalytic protocols due to the importance of the enantioenriched products. However, current strategies rely on the temporal separation of catalytic cycles to circumvent incompatibilities, precluding photobiocatalytic transformations that require the in situ generation of reactive intermediates. We report a single-step cyclic deracemization protocol by combining a water-soluble photocatalyst (sodium anthraquinone-2-sulfonate) with a promiscuous alcohol dehydrogenase (Geotrichum candidum acetophenone reductase) encapsulated in lyophilized microbial whole-cells. Insights into enzyme selectivity and system dynamics from molecular docking and kinetic modeling guided the optimization of the multi-component system. Our approach represents a modular and generalizable strategy for developing photobiocatalytic cascades operating under mutually compatible conditions, wherein spatial separation mitigates photodamage and enables simultaneous dual catalytic turnover.

Keywords

deracemization
photocatalysis
biocatalysis
photobiocatalysis
whole-cell

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Supplementary information to support publication including experimental procedures and characterization data
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.