Publication

Computational redesign of enzymes for regio- and enantioselective hydroamination

Li, R., Wijma, H. J., Song, L., Cui, Y., Otzen, M., Tian, Y., Du, J., Li, T., Niu, D., Chen, Y., Feng, J., Han, J., Chen, H., Tao, Y., Janssen, D. B. & Wu, B., 21-May-2018, In : Nature Chemical Biology. 14, p. 664-670

Research output: Contribution to journalArticleAcademicpeer-review

APA

Li, R., Wijma, H. J., Song, L., Cui, Y., Otzen, M., Tian, Y., ... Wu, B. (2018). Computational redesign of enzymes for regio- and enantioselective hydroamination. Nature Chemical Biology, 14, 664-670. https://doi.org/10.1038/s41589-018-0053-0

Author

Li, Ruifeng ; Wijma, Hein J ; Song, Lu ; Cui, Yinglu ; Otzen, Marleen ; Tian, Yu'e ; Du, Jiawei ; Li, Tao ; Niu, Dingding ; Chen, Yanchun ; Feng, Jing ; Han, Jian ; Chen, Hao ; Tao, Yong ; Janssen, Dick B ; Wu, Bian. / Computational redesign of enzymes for regio- and enantioselective hydroamination. In: Nature Chemical Biology. 2018 ; Vol. 14. pp. 664-670.

Harvard

Li, R, Wijma, HJ, Song, L, Cui, Y, Otzen, M, Tian, Y, Du, J, Li, T, Niu, D, Chen, Y, Feng, J, Han, J, Chen, H, Tao, Y, Janssen, DB & Wu, B 2018, 'Computational redesign of enzymes for regio- and enantioselective hydroamination', Nature Chemical Biology, vol. 14, pp. 664-670. https://doi.org/10.1038/s41589-018-0053-0

Standard

Computational redesign of enzymes for regio- and enantioselective hydroamination. / Li, Ruifeng; Wijma, Hein J; Song, Lu; Cui, Yinglu; Otzen, Marleen; Tian, Yu'e; Du, Jiawei; Li, Tao; Niu, Dingding; Chen, Yanchun; Feng, Jing; Han, Jian; Chen, Hao; Tao, Yong; Janssen, Dick B; Wu, Bian.

In: Nature Chemical Biology, Vol. 14, 21.05.2018, p. 664-670.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Li R, Wijma HJ, Song L, Cui Y, Otzen M, Tian Y et al. Computational redesign of enzymes for regio- and enantioselective hydroamination. Nature Chemical Biology. 2018 May 21;14:664-670. https://doi.org/10.1038/s41589-018-0053-0


BibTeX

@article{c6cd8cda176d4c49bf8dd4a979dea30e,
title = "Computational redesign of enzymes for regio- and enantioselective hydroamination",
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 synthesis of pharmaceuticals and bioactive compounds. Without a requirement for further optimization by laboratory evolution, the redesigned enzymes exhibit substrate tolerance up to a concentration of 300 g/L, conversion up to 99{\%}, β-regioselectivity >99{\%} and product enantiomeric excess >99{\%}. The results highlight the use of computational design to rapidly adapt an enzyme to industrially viable reactions.",
author = "Ruifeng Li and Wijma, {Hein J} and Lu Song and Yinglu Cui and Marleen Otzen and Yu'e Tian and Jiawei Du and Tao Li and Dingding Niu and Yanchun Chen and Jing Feng and Jian Han and Hao Chen and Yong Tao and Janssen, {Dick B} and Bian Wu",
year = "2018",
month = "5",
day = "21",
doi = "10.1038/s41589-018-0053-0",
language = "English",
volume = "14",
pages = "664--670",
journal = "Nature Chemical Biology",
issn = "1552-4469",

}

RIS

TY - JOUR

T1 - Computational redesign of enzymes for regio- and enantioselective hydroamination

AU - Li, Ruifeng

AU - Wijma, Hein J

AU - Song, Lu

AU - Cui, Yinglu

AU - Otzen, Marleen

AU - Tian, Yu'e

AU - Du, Jiawei

AU - Li, Tao

AU - Niu, Dingding

AU - Chen, Yanchun

AU - Feng, Jing

AU - Han, Jian

AU - Chen, Hao

AU - Tao, Yong

AU - Janssen, Dick B

AU - Wu, Bian

PY - 2018/5/21

Y1 - 2018/5/21

N2 - 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 synthesis of pharmaceuticals and bioactive compounds. Without a requirement for further optimization by laboratory evolution, the redesigned enzymes exhibit substrate tolerance up to a concentration of 300 g/L, conversion up to 99%, β-regioselectivity >99% and product enantiomeric excess >99%. The results highlight the use of computational design to rapidly adapt an enzyme to industrially viable reactions.

AB - 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 synthesis of pharmaceuticals and bioactive compounds. Without a requirement for further optimization by laboratory evolution, the redesigned enzymes exhibit substrate tolerance up to a concentration of 300 g/L, conversion up to 99%, β-regioselectivity >99% and product enantiomeric excess >99%. The results highlight the use of computational design to rapidly adapt an enzyme to industrially viable reactions.

U2 - 10.1038/s41589-018-0053-0

DO - 10.1038/s41589-018-0053-0

M3 - Article

C2 - 29785057

VL - 14

SP - 664

EP - 670

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4469

ER -

ID: 61152759