Engineering Enzyme Substrate Scope Complementarity for Promiscuous Cascade Synthesis of 1,2‐Amino Alcohols
Abstract: Biocatalytic cascades are uniquely powerful for the efficient, asymmetric synthesis of bioactive compounds. However, high substrate specificity can hinder the scope of biocatalytic cascades because the constituent enzymes may have non‐complementary activity. In this study, we implemented a substrate multiplexed screening (SUMS) based directed evolution approach to improve the substrate scope overlap between a transaldolase (ObiH) and a decarboxylase for the production of chiral 1,2‐amino alcohols. To generate a promiscuous cascade, we engineered a tryptophan decarboxylase to act efficiently on β‐OH amino acids while avoiding activity on l‐threonine, which is needed for ObiH activity. We leveraged this exquisite selectivity with matched substrate scope to produce a variety of enantiopure 1,2‐amino alcohols in a one‐pot cascade from aldehydes or styrene oxides. This demonstration shows how SUMS can be used to guide the development of promiscuous, C−C bond forming cascades.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Engineering Enzyme Substrate Scope Complementarity for Promiscuous Cascade Synthesis of 1,2‐Amino Alcohols ; day:18 ; month:10 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (18.10.2022) (gesamt 1)
- Creator
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McDonald, Allwin D.
Bruffy, Samantha K.
Kasat, Aadhishre T.
Buller, Andrew R.
- DOI
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10.1002/anie.202212637
- URN
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urn:nbn:de:101:1-2022101915204278954899
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:34 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- McDonald, Allwin D.
- Bruffy, Samantha K.
- Kasat, Aadhishre T.
- Buller, Andrew R.
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