9fd7
From Proteopedia
Re-engineered peroxygenase variant of 2-deoxy-D-ribose-5-phosphate aldolase in substrate-free state
Structural highlights
FunctionDEOC_ECOLC Catalyzes a reversible aldol reaction between acetaldehyde and D-glyceraldehyde 3-phosphate to generate 2-deoxy-D-ribose 5-phosphate. Publication Abstract from PubMedThe enzyme 2-deoxy-D-ribose-5-phosphate aldolase (DERA) naturally catalyzes the reversible aldol addition between acetaldehyde and D-glyceraldehyde-3-phosphate to yield 2-deoxy-D-ribose-5-phosphate. Herein we describe the redesign of DERA into a proficient non-natural peroxygenase that promotes the asymmetric epoxidation of various alpha,beta-unsaturated aldehydes. This repurposed aldolase, named DERA-EP, is able to utilize H(2)O(2) to accomplish both anti- and syn-selective epoxidations of various alpha,beta-unsaturated aldehydes to give the corresponding epoxides with moderate to high diastereoselectivity (diastereomeric ratio up to 99 : 1) and excellent enantioselectivity (enantiomeric ratio up to 99 : 1). Crystallographic analysis of DERA-EP in a substrate-free and substrate-bound state provides a structural context for the evolved activity, a clear explanation for the high enantioselectivity, and compelling evidence for catalysis via enzyme-bound iminium ion intermediates. The unprecedented anti-selectivity of DERA-EP with multiple alpha,beta-unsaturated aldehydes is complementary to the syn-selectivity of previously reported enzyme-, metal- and organo-catalysts, making DERA-EP an attractive new asset to the toolbox of epoxidation catalysts. Engineering 2-Deoxy-D-ribose-5-phosphate Aldolase for anti- and syn-Selective Epoxidations of alpha,beta-Unsaturated Aldehydes.,Zhou H, Kunzendorf A, Xu G, Frietema HOT, Thunnissen AWH, Poelarends GJ Angew Chem Int Ed Engl. 2025 Feb 24:e202503054. doi: 10.1002/anie.202503054. PMID:39993220[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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