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Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein

Cho, Inha and Prier, Christopher K. and Jia, Zhi-Jun and Zhang, Ruijie K. and Görbe, Tamás and Arnold, Frances H. (2019) Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein. Angewandte Chemie International Edition, 58 (10). pp. 3138-3142. ISSN 1433-7851. http://resolver.caltech.edu/CaltechAUTHORS:20190102-135256908

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Abstract

Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O‐pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron‐nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/anie.201812968DOIArticle
ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2019 WILEY‐VCH Verlag. Manuscript received: November 12, 2018; Accepted manuscript online: January 2, 2019; Version of record online: January 25, 2019. We thank Kai Chen and Dr. Xiongyi Huang for helpful discussions and assistance with ee determination. We also thank X. H. and Dr. Sabine Brinkmann‐Chen for proofreading the manuscript. We acknowledge the National Science Foundation, Division of Molecular and Cellular Biosciences (grant MCB‐1513007) for supporting this work. C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. R.K.Z. was supported by a National Science Foundation Graduate Research Fellowship (DGE‐1144469), the Caltech Biotechnology Leadership Program, and the Donna and Benjamin M. Rosen Bioengineering Center. Z.‐J.J. is supported by the Deutsche Forschungsgemeinschaft (JI 289/1‐1). T.G. thanks for the financial support of the Stiftelsen Olle Engkvist Byggmästare and the Kungl. Skogs‐och Lantbruksakademien. The authors declare no conflict of interest.
Group:Resnick Sustainability Institute, Rosen Bioengineering Center
Funders:
Funding AgencyGrant Number
NSFMCB-1513007
Resnick Sustainability InstituteUNSPECIFIED
NSF Graduate Research FellowshipDGE-1144469
Caltech Biotechnology Leadership ProgramUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)JI 289/1‐1
Stiftelsen Olle Engkvist ByggmästareUNSPECIFIED
Kungl. Skogs-och LantbruksakademienUNSPECIFIED
Subject Keywords:alkenes; amino alcohols; biocatalysis; directed evolution; heme proteins; nitrenes
Record Number:CaltechAUTHORS:20190102-135256908
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190102-135256908
Official Citation:I. Cho, C. K. Prier, Z.-J. Jia, R. K. Zhang, T. Görbe, F. H. Arnold, Angew. Chem. Int. Ed. 2019, 58, 3138. doi: 10.1002/anie.201812968
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91992
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:03 Jan 2019 15:40
Last Modified:15 May 2019 16:27

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