Current state of and need for enzyme engineering of 2-deoxy-D-ribose 5-phosphate aldolases and its impact.
Aldolase
Applications
Biocatalysis
C–C bond formation
DERA
Protein engineering
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
16
04
2021
accepted:
19
07
2021
revised:
13
07
2021
pubmed:
20
8
2021
medline:
1
9
2021
entrez:
19
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34410440
doi: 10.1007/s00253-021-11462-0
pii: 10.1007/s00253-021-11462-0
pmc: PMC8403123
doi:
Substances chimiques
Ribosemonophosphates
0
ribose-5-phosphate
4B2428FLTO
Aldehyde-Lyases
EC 4.1.2.-
Fructose-Bisphosphate Aldolase
EC 4.1.2.13
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
6215-6228Informations de copyright
© 2021. The Author(s).
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