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Engineered Cytochrome c-Catalyzed Lactone-Carbene B–H Insertion

Chen, Kai and Huang, Xiongyi and Zhang, Shuo-Qing and Zhou, Andrew Z. and Kan, S. B. Jennifer and Hong, Xin and Arnold, Frances H. (2019) Engineered Cytochrome c-Catalyzed Lactone-Carbene B–H Insertion. Synlett, 30 (4). pp. 378-382. ISSN 0936-5214. PMCID PMC6436545. http://resolver.caltech.edu/CaltechAUTHORS:20190122-134051110

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Abstract

Previous work has demonstrated that variants of a heme protein, Rhodothermus marinus cytochrome c (Rma cyt c), catalyze abiological carbene boron–hydrogen (B–H) bond insertion with high efficiency and selectivity. Here we investigated this carbon–boron bond-forming chemistry with cyclic, lactone-based carbenes. Using directed evolution, we obtained a Rma cyt c variant BOR^(LAC) that shows high selectivity and efficiency for B–H insertion of 5- and 6-membered lactone carbenes (up to 24,500 total turnovers and 97.1:2.9 enantiomeric ratio). The enzyme shows low activity with a 7-membered lactone carbene. Computational studies revealed a highly twisted geometry of the 7-membered lactone carbene intermediate relative to 5- and 6-membered ones. Directed evolution of cytochrome c together with computational characterization of key iron-carbene intermediates has allowed us to expand the scope of enzymatic carbene B–H insertion to produce new lactone-based organoborons.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1055/s-0037-1611662DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436545PubMed CentralArticle
ORCID:
AuthorORCID
Chen, Kai0000-0002-3325-3536
Huang, Xiongyi0000-0001-7156-8881
Zhang, Shuo-Qing0000-0002-7617-3042
Kan, S. B. Jennifer0000-0001-6371-8042
Hong, Xin0000-0003-4717-2814
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2019 Georg Thieme Verlag Stuttgart. Copyright with the author. CC BY ND NC 4.0. Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue. Financial support from the NSF Division of Molecular and Cellular Biosciences grant MCB-1513007, National Natural Science Foundation of China (21702182), Zhejiang University, the Chinese “Thousand Youth Talents Plan”, and the “Fundamental Research Funds for the Central Universities” is gratefully acknowledged. K.C. thanks the Resnick Sustainability Institute at Caltech for fellowship support. X.H. is supported by an NIH pathway to independence award (grant K99GM129419). A.Z.Z. thanks the Caltech SURF program. Calculations were performed on the high-performance computing system at the Department of Chemistry, Zhejiang University. We thank R. D. Lewis and R. K. Zhang for helpful discussions and comments. We also thank the Caltech Mass Spectrometry Laboratory.
Group:Resnick Sustainability Institute
Funders:
Funding AgencyGrant Number
NSFMCB-1513007
National Natural Science Foundation of China21702182
Zhejiang UniversityUNSPECIFIED
1000 Young Talents ProgramUNSPECIFIED
Fundamental Research Funds for the Central UniversitiesUNSPECIFIED
Resnick Sustainability InstituteUNSPECIFIED
NIHK99GM129419
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Subject Keywords:cytochrome c; carbene; organoboron; lactones; biocatalyst; directed evolution
PubMed Central ID:PMC6436545
Record Number:CaltechAUTHORS:20190122-134051110
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190122-134051110
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92402
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Jan 2019 21:50
Last Modified:29 Mar 2019 16:07

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