Efficient chemoenzymatic synthesis of α-aryl aldehydes as intermediates in C-C bond forming biocatalytic cascades.
ACS Catal
; 12(17): 10700-10710, 2022 Sep 02.
Article
en En
| MEDLINE
| ID: mdl-36420479
ABSTRACT
Multi-enzyme biocatalytic cascades are emerging as practical routes for the synthesis of complex bioactive molecules. However, the relative sparsity of water-stable carbon electrophiles limits the synthetic complexity of molecules made from such cascades. Here, we develop a chemoenzymatic platform that leverages styrene oxide isomerase (SOI) to covert readily accessible aryl epoxides into α-aryl aldehydes through a Meinwald rearrangement. These unstable aldehyde intermediates are then intercepted with a C-C bond forming enzyme, ObiH, that catalyzes a transaldolase reaction with l-threonine to yield synthetically challenging ß-hydroxy-α-amino acids. Co-expression of both enzymes in E. coli yields a whole cell biocatalyst capable of synthesizing a variety of stereopure non-standard amino acids (nsAA) and can be produced on gram-scale. We used isotopically labelled substrates to probe the mechanism of SOI, which we show catalyzes a concerted isomerization featuring a stereospecific 1,2-hydride shift. The viability of in situ generated α-aryl aldehydes was further established by intercepting them with a recently engineered decarboxylative aldolase to yield γ-hydroxy nsAAs. Together, these data establish a versatile method of producing α-aryl aldehydes in simple, whole cell conditions and show that these intermediates are useful synthons in CâC bond forming cascades.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
ACS Catal
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos