Asymmetric assembly of aldose carbohydrates from formaldehyde and glycolaldehyde by tandem biocatalytic aldol reactions.
The preparation of multifunctional chiral molecules can be greatly simplified by adopting a route via the sequential catalytic assembly of achiral building blocks. The catalytic aldol assembly of prebiotic compounds into stereodefined pentoses and hexoses is an as yet unmet challenge. Such a process would be of remarkable synthetic utility and highly significant with regard to the origin of life. Pursuing an expedient enzymatic approach, here we use engineered D-fructose-6-phosphate aldolase from Escherichia coli to prepare a series of three- to six-carbon aldoses by sequential one-pot additions of glycolaldehyde. Notably, the pertinent selection of the aldolase variant provides control of the sugar size. The stereochemical outcome of the addition was also altered to allow the synthesis of L-glucose and related derivatives. Such engineered biocatalysts may offer new routes for the straightforward synthesis of natural molecules and their analogues that circumvent the intricate enzymatic pathways forged by evolution.
Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Anna
A
Szekrenyi
Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Xavier
X
Garrabou
Depatment Química. Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Teodor
T
Parella
Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Jesús
J
Joglar
Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Jordi
J
Bujons
Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Pere
P
Clapés
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000446:Aldehyde-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry*; D001665:Binding Sites; D055162:Biocatalysis; D020134:Catalytic Domain; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005557:Formaldehyde / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism*; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013237:Stereoisomerism
D000447:Aldehydes; D029968:Escherichia coli Proteins; D009005:Monosaccharides; D011994:Recombinant Proteins; D005557:Formaldehyde; C116609:3-hydroxybutanal; D000446:Aldehyde-Lyases; C426024:fsaA protein, E coli; D000079:Acetaldehyde; C010972:glycolaldehyde