Rational Enzyme Design without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases

David Teze, Jiao Zhao, Mathias Wiemann, Zubaida G. A. Kazi, Rossana Lupo, Birgitte Zeuner, Marlène Vuillemin, Mette E. Rønne, Göran Carlström, Jens Ø. Duus, Yves-Henri Sanejouand, Michael J. O'Donohue, Eva Nordberg Karlsson, Régis Fauré, Henrik Stålbrand, Birte Svensson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

2 Citeringar (SciVal)

Sammanfattning

Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering is useful to remedy this, but it usually requires prior structural knowledge of the target enzyme, and/or relies on extensive, time-consuming screening and analysis. Here we describe a straightforward strategy that involves rational rapid in silico analysis of protein sequences. The method pinpoints 6-12 single mutant candidates to improve transglycosylation yields. Requiring very little prior knowledge of the target enzyme other than its sequence, the method is generic and procures catalysts for the formation of glycosidic bonds involving various d / l -, α/β-pyranosides or furanosides, and exo - and endo -action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.

Originalspråkengelska
Sidor (från-till)10323-10334
TidskriftChemistry: A European Journal
Volym27
Utgåva40
Tidigt onlinedatum2021 apr 29
DOI
StatusPublished - 2021

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi

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