Issue 29, 2025

Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives

Abstract

Phosphorylated myo-inositols (InsPs) are essential cytoplasmic signaling molecules, while their lipidated analogs (PtdInsPs) play a crucial role in membrane signaling. Stereoselective synthesis of these compounds has been achieved through various methods, predominantly using the meso compound myo-inositol as a starting material. However, phytate (InsP6), also a meso compound, is the most abundant inositol derivative in plants – far more prevalent than myo-inositol itself. Despite its abundance, phytate has been rarely used in synthetic strategies for accessing a variety of chiral inositol phosphates and their derivatives through selective dephosphorylations on a preparative scale. Here, we report gram-scale (stereo)selective dephosphorylations of phytate using phytases and demonstrate the application of these products in generating modified InsPs through a transient phosphitylation approach. Notably, the bacterial effector XopH efficiently desymmetrizes meso-phytate to yield enantiomerically pure 1-OH-InsP5. This transformation renders the 1-position accessible for further modifications, which, in biological systems, is where glycerolphosphate diesters are attached. By using selective dephosphorylations with phytases in concert with chemoselective telescoping reaction sequences, this approach greatly advances the stereoselective synthesis of inositol phosphates and their derivatives, such as glycerophosphoinositols, from abundant InsP6.

Graphical abstract: Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives

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Article information

Article type
Edge Article
Submitted
18 Apr 2025
Accepted
20 Jun 2025
First published
23 Jun 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2025,16, 13459-13467

Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives

G. M. Häner, G. Liu, E. Lange, N. Jork, K. Ditrich, R. Greiner, G. Schaaf and H. J. Jessen, Chem. Sci., 2025, 16, 13459 DOI: 10.1039/D5SC02844B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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