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.
Original language | English |
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Pages (from-to) | 664-670 |
Journal | Nature Chemical Biology |
Volume | 14 |
Early online date | 2018 |
DOIs | |
Publication status | Published - 21-May-2018 |
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Computer hertekent enzym
Janssen, D. & Wijma, H.
22/05/2018
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Redesigning Enzymes, via Computer
Janssen, D. & Wijma, H.
22/05/2018
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Computer redesigns enzyme
Janssen, D. & Wijma, H.
21/05/2018
1 item of Media coverage
Press/Media: Public Engagement Activities › Popular