Abstract
Deoxyribose-5-phosphate aldolases (DERAs, EC 4.1.2.4) are acetaldehyde-dependent, Class I aldolases catalyzing in nature a reversible aldol reaction between an acetaldehyde donor (C2 compound) and glyceraldehyde-3-phosphate acceptor (C3 compound, C3P) to generate deoxyribose-5-phosphate (C5 compound, DR5P). DERA enzymes have been found to accept also other types of aldehydes as their donor, and in particular as acceptor molecules. Consequently, DERA enzymes can be applied in C–C bond formation reactions to produce novel compounds, thus offering a versatile biocatalytic alternative for synthesis. DERA enzymes, found in all kingdoms of life, share a common TIM barrel fold despite the low overall sequence identity. The catalytic mechanism is well-studied and involves formation of a covalent enzyme-substrate intermediate. A number of protein engineering studies to optimize substrate specificity, enzyme efficiency, and stability of DERA aldolases have been published. These have employed various engineering strategies including structure-based design, directed evolution, and recently also machine learning–guided protein engineering. For application purposes, enzyme immobilization and usage of whole cell catalysis are preferred methods as they improve the overall performance of the biocatalytic processes, including often also the stability of the enzyme. Besides single-step enzymatic reactions, DERA aldolases have also been applied in multi-enzyme cascade reactions both in vitro and in vivo. The DERA-based applications range from synthesis of commodity chemicals and flavours to more complicated and high-value pharmaceutical compounds.Key points• DERA aldolases are versatile biocatalysts able to make new C–C bonds.• Synthetic utility of DERAs has been improved by protein engineering approaches.• Computational methods are expected to speed up the future DERA engineering efforts.Graphical abstract
Highlights
Enzymatic C–C bond formation reactions offer a means to build up the carbon backbone and synthesize important organic compounds
The current review focuses in particular on 2deoxyribose-5-phosphate aldolases (DERA, EC 4.1.2.4), Appl Microbiol Biotechnol (2021) 105:6215–6228 which are widespread cytosolic enzymes involved in the catabolism of the pentose motif of deoxynucleosides in the pentose phosphate pathway and do not require any cofactor for their activity (Tozzi et al 2006)
There are already many examples where DERA has been utilized in stereoselective enzyme-assisted synthesis of commodity chemicals, flavours, and building blocks for pharmaceutical drug molecules
Summary
Enzymatic C–C bond formation reactions offer a means to build up the carbon backbone and synthesize important organic compounds. DERA enzymes belong to so called Class I aldolases and catalyze a reaction for which both of the substrates and the product are aldehydes, i.e. the reaction between 2-deoxy-D-ribose-5-phosphate (DR5P) and Dglyceraldehyde-3-phosphate (G3P) + acetaldehyde (C2) (Fig. 1B). In this reversible reaction, C–C bond is either cleaved (retroaldol reaction) or formed (aldol reaction) (Fig. 1A). Protein engineering offers a means to affect the enzyme properties, such as substrate promiscuity and catalytic rate, to optimize or invert stereoselectivity, and to improve stability under certain conditions or release inhibition Recent developments in this field concerning DERA aldolases are the scope of this review
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
