ABSTRACT Introduction of innovative biocatalytic processes offers great promise for applications in green chemistry. However, owing to limited catalytic performance, the enzymes harvested

from nature's biodiversity often need to be improved for their desired functions by time-consuming iterative rounds of laboratory evolution. Here we describe the use of structure-based

computational enzyme design to convert _Bacillus_ sp. YM55-1 aspartase, an enzyme with a very narrow substrate scope, to a set of complementary hydroamination biocatalysts. The redesigned

enzymes catalyze asymmetric addition of ammonia to substituted acrylates, affording enantiopure aliphatic, polar and aromatic Β-amino acids that are valuable building blocks for the

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support SIMILAR CONTENT BEING VIEWED BY OTHERS BIOCATALYTIC SYNTHESIS OF NON-STANDARD AMINO ACIDS BY A DECARBOXYLATIVE ALDOL REACTION Article 21 February 2022 DEVELOPMENT OF A VERSATILE AND

EFFICIENT C–N LYASE PLATFORM FOR ASYMMETRIC HYDROAMINATION VIA COMPUTATIONAL ENZYME REDESIGN Article 29 April 2021 ENGINEERING AN EFFICIENT AND ENANTIOSELECTIVE ENZYME FOR THE

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Google Scholar  Download references ACKNOWLEDGEMENTS We thank W. Szymanski for discussions. We thank for the 100 Talent Program grant (B.W.) and Biological Resources Service Network

Initiative (ZSYS-012; B.W.) and a grant (SKT1604; C.Y.L.) from the Chinese Academy of Sciences, Natural Science Foundation of China grants (31601412 (B.W.), 21603013 (C.Y.L.)), and a

BE-Basic grant (H.J.W. and D.B.J.) from the Dutch Ministry of Economic Affairs for the financial support. AUTHOR INFORMATION Author notes * These authors contributed equally: Ruifeng Li,

Hein J., Lu Song. AUTHORS AND AFFILIATIONS * CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology,

Chinese Academy of Sciences, Beijing, China Ruifeng Li, Lu Song, Yinglu Cui, Yu’e Tian, Jiawei Du, Tao Li, Dingding Niu, Yanchun Chen, Jing Feng, Jian Han, Hao Chen, Yong Tao & Bian Wu *

State Key Laboratory of Transducer Technology, Chinese Academy of Sciences, Beijing, China Ruifeng Li & Yinglu Cui * University of Chinese Academy of Sciences, Beijing, China Ruifeng

Li, Jiawei Du, Tao Li, Yanchun Chen & Jing Feng * Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The

Netherlands Hein J. Wijma, Marleen Otzen & Dick B. Janssen Authors * Ruifeng Li View author publications You can also search for this author inPubMed Google Scholar * Hein J. Wijma View

author publications You can also search for this author inPubMed Google Scholar * Lu Song View author publications You can also search for this author inPubMed Google Scholar * Yinglu Cui

View author publications You can also search for this author inPubMed Google Scholar * Marleen Otzen View author publications You can also search for this author inPubMed Google Scholar *

Yu’e Tian View author publications You can also search for this author inPubMed Google Scholar * Jiawei Du View author publications You can also search for this author inPubMed Google

Scholar * Tao Li View author publications You can also search for this author inPubMed Google Scholar * Dingding Niu View author publications You can also search for this author inPubMed 

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inPubMed Google Scholar * Jian Han View author publications You can also search for this author inPubMed Google Scholar * Hao Chen View author publications You can also search for this

author inPubMed Google Scholar * Yong Tao View author publications You can also search for this author inPubMed Google Scholar * Dick B. Janssen View author publications You can also search

for this author inPubMed Google Scholar * Bian Wu View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS D.B.J. and B.W. initiated the project.

B.W., H.J.W. and Y. Cui performed the computational work. L.S., R.L., M.O., Y. Tian, J.D., T.L., D.N., Y. Chen and J.F. performed biocatalytic experiments. J.H., H.C. and Y. Tao developed

high-density fermentation methods. R.L. performed preparative-scale synthesis of the amino acids. D.B.J. and B.W. provided supervision and input on experimental design and wrote the

manuscript, which was revised and approved by all authors. R.L., H.J.W. and L.S. contributed equally to this work. CORRESPONDING AUTHORS Correspondence to Dick B. Janssen or Bian Wu. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional

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RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, R., Wijma, H.J., Song, L. _et al._ Computational redesign of enzymes for regio- and enantioselective

hydroamination. _Nat Chem Biol_ 14, 664–670 (2018). https://doi.org/10.1038/s41589-018-0053-0 Download citation * Received: 14 October 2017 * Accepted: 09 March 2018 * Published: 21 May 2018

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