Aldolases
Aldol reactions are cornerstones of organic synthetic chemistry as they enable the formation of new carbon-carbon bonds while forming new stereocenters. Aldol reactions are used in the synthesis of a variety of hydroxylated compounds which are of particular interest in the synthesis of bioactive substances and can be formed from α-hydroxylated ketones and aldehydes.
Biocatalytic synthesis of aldols, using aldolase enzymes, would bring several advantages over traditional synthetic methods:
(1) the catalytic capacity of enzymes far exceeds many traditionally used organic or organometallic catalysts.
(2) enzymes are fully biodegradable, harmless to handle and work in aqueous solutions.
(3) they offer lower energy consumption as reactions can be performed with high efficiency at ambient temperatures.
(4) the atomic economy can be optimized while synthesis steps can be minimized as protecting groups usually do not need to be used.
(5) enzymes exhibit stereoselectivity that allows asymmetric synthesis.
Our studies of aldolases therefore aim to ...
- broaden the substrate selectivity to include non-phosphorylated reactant substrates.
- deepen the understanding of structure / activity relationships in aldolase-catalyzed reactions.
Publications
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Engineering aldolases for asymmetric synthesis
Part of Methods in Enzymology, p. 149-167, 2020.
Article in journal
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Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones
Part of Journal of Organic Chemistry, p. 6982-6991, 2019.
Article in journal
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Al-Smadi, Derar
Carboligation using the aldol reaction: A comparison of stereoselectivity and methods
2018.
Doctoral thesis, comprehensive summary
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New Stereoselective Biocatalysts for Carboligation and Retro-Aldol Cleavage Reactions Derived from D-Fructose 6-Phosphate Aldolase
Part of Biochemistry, p. 5877-5885, 2018.
Article in journal
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Synthesis of substrates for aldolase-catalyzed reactions: A comparison of methods for the synthesis of substituted phenylacetaldehydes
Part of Synlett, p. 1187-1190, 2018.
Article in journal
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Linking coupled motions and entropic effects to the catalytic activity of 2-deoxyribose-5-phosphate aldolase (DERA)
Part of Chemical Science, p. 1415-1421, 2016.
Article in journal
DOI for Linking coupled motions and entropic effects to the catalytic activity of 2-deoxyribose-5-phosphate aldolase (DERA) Download full text (pdf) of Linking coupled motions and entropic effects to the catalytic activity of 2-deoxyribose-5-phosphate aldolase (DERA)
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A micro-plate format assay for real-time screening for new aldolases accepting aryl-substituted acceptor substrates
Part of ChemBioChem (Print), p. 2595-2598, 2015.
Article in journal
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Ma, Huan
Aldolases for Enzymatic Carboligation: Directed Evolution and Enzyme Structure-Function Relationship Studies
2015.
Doctoral thesis, comprehensive summary