{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Meza A"],"funding":["NIGMS NIH HHS"],"pagination":["10700-10710"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9681013"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(17)"],"pubmed_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 β-hydroxy-α-amino acids. Co-expression of both enzymes in <i>E. coli</i> yields a whole cell biocatalyst capable of synthesizing a variety of stereopure non-standard amino acids (nsAA) and can be produced on <i>gram</i>-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 <i>in situ</i> 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 C‒C bond forming cascades."],"journal":["ACS catalysis"],"pubmed_title":["Efficient chemoenzymatic synthesis of α-aryl aldehydes as intermediates in C-C bond forming biocatalytic cascades."],"pmcid":["PMC9681013"],"funding_grant_id":["DP2 GM137417"],"pubmed_authors":["Grieger AM","Campbell ME","McGill MJ","Thein SA","Zmich A","Meza A","Willoughby PH","Buller AR"],"additional_accession":[]},"is_claimable":false,"name":"Efficient chemoenzymatic synthesis of α-aryl aldehydes as intermediates in C-C bond forming biocatalytic cascades.","description":"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 β-hydroxy-α-amino acids. Co-expression of both enzymes in <i>E. coli</i> yields a whole cell biocatalyst capable of synthesizing a variety of stereopure non-standard amino acids (nsAA) and can be produced on <i>gram</i>-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 <i>in situ</i> 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 C‒C bond forming cascades.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-19T16:11:52.235Z","creation":"2025-04-19T16:11:52.235Z"},"accession":"S-EPMC9681013","cross_references":{"pubmed":["36420479"],"doi":["10.1021/acscatal.2c02369"]}}