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Published on: November 30, 2021
Chemogenetic Manipulation of H2S with Spatiotemporal Precision
Asal Ghaffari Zaki1,2, Hamzah Issa1,2, Seyed Mohammad Miri1
1Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul 34810, Türkiye.
Abstract:
Hydrogen sulfide (H2S) is a signaling molecule with a plethora of biological functions, yet precision tools for modulating its intracellular flux remain scarce. Conventional small-molecule donors and enzymatic systems often suffer from off-target reactivity, uncontrolled release kinetics, and redox crosstalk, confounding mechanistic studies. Here, we establish a Salmonella typhimurium d-cysteine desulfhydrase (stDCyD)-derived chemogenetic tool for controlled H2S manipulation in living cells. stDCyD catalyzes the α,β-elimination of d-cysteine to selectively yield bioavailable H2S. We term this tool H2SWITCH. Our approach exhibits pronounced enantioselectivity for d-cysteine, robust catalytic efficiency at physiological temperatures, and temporal tunability through substrate dosing. This chemogenetic tool provides a chemically defined and interference-free method to unravel the physiological and pathological roles of H2S with unprecedented precision in complex biological systems.
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