Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
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.
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.Attached Files
Supplemental Material - anie201812968-s1-supporting_information.pdf
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Additional details
- Eprint ID
- 91992
- Resolver ID
- CaltechAUTHORS:20190102-135256908
- NSF
- MCB-1513007
- Resnick Sustainability Institute
- NSF Graduate Research Fellowship
- DGE-1144469
- Caltech Biotechnology Leadership Program
- Donna and Benjamin M. Rosen Bioengineering Center
- Deutsche Forschungsgemeinschaft (DFG)
- JI 289/1‐1
- Stiftelsen Olle Engkvist Byggmästare
- Kungl. Skogs-och Lantbruksakademien
- Created
-
2019-01-03Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field
- Caltech groups
- Resnick Sustainability Institute, Rosen Bioengineering Center