Optical control of sphingolipid biosynthesis using photoswitchable sphingosines

Area of Science:

• Biochemistry
• Cell Biology
• Chemical Biology

Background:

• Sphingolipid metabolism is a complex network regulating vital cellular processes.
• Intermediates are often short-lived with opposing biological activities, complicating research.
• Understanding sphingolipid roles requires precise control over their synthesis.

Purpose of the Study:

• To develop novel tools for precise, light-controlled manipulation of sphingolipid biosynthesis.
• To investigate the impact of light-induced structural changes on sphingolipid metabolic conversion.
• To establish a method for spatiotemporal control over sphingolipid production in living cells.

Main Methods:

• Synthesis of clickable, azobenzene-containing sphingosines (caSphs).
• In vitro enzyme assays and metabolic labeling studies.
• Photo-isomerization of caSphs to induce trans-to-cis conformational changes.

Main Results:

• Trans-to-cis isomerization of caSphs significantly stimulates their conversion by ceramide and sphingomyelin synthases.
• Light-induced changes in sphingolipid production are acute and reversible.
• caSphs can be efficiently implemented in living cells for light-controlled sphingolipid synthesis.

Conclusions:

• caSphs serve as versatile, light-sensitive substrates for sphingolipid biosynthesis.
• This technology allows for spatiotemporal control over sphingolipid metabolism with high precision.
• caSphs offer novel avenues for studying sphingolipid function and cellular regulation.