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

Teze, David ; Zhao, Jiao ; Wiemann, Mathias LU ; Kazi, Zubaida G. A. ; Lupo, Rossana ; Zeuner, Birgitte ; Vuillemin, Marlène ; Rønne, Mette E. ; Carlström, Göran LU orcid and Duus, Jens Ø. , et al. (2021) In Chemistry: A European Journal 27(40). p.10323-10334
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Chemistry: A European Journal
volume
27
issue
40
pages
10323 - 10334
publisher
Wiley-Blackwell
external identifiers
  • scopus:85107290185
  • pmid:33914359
ISSN
1521-3765
DOI
10.1002/chem.202100110
language
English
LU publication?
yes
id
b604f553-a061-4dff-a8b2-636f3cd66acd
date added to LUP
2021-05-26 22:12:24
date last changed
2024-06-29 12:41:21
@article{b604f553-a061-4dff-a8b2-636f3cd66acd,
  abstract     = {{<p>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 <i>exo </i>- and <i>endo </i>-action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.</p>}},
  author       = {{Teze, David and Zhao, Jiao and Wiemann, Mathias and Kazi, Zubaida G. A. and Lupo, Rossana and Zeuner, Birgitte and Vuillemin, Marlène and Rønne, Mette E. and Carlström, Göran and Duus, Jens Ø. and Sanejouand, Yves-Henri and O'Donohue, Michael J. and Karlsson, Eva Nordberg and Fauré, Régis and Stålbrand, Henrik and Svensson, Birte}},
  issn         = {{1521-3765}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{40}},
  pages        = {{10323--10334}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Chemistry: A European Journal}},
  title        = {{Rational Enzyme Design without Structural Knowledge : A Sequence-Based Approach for Efficient Generation of Transglycosylases}},
  url          = {{http://dx.doi.org/10.1002/chem.202100110}},
  doi          = {{10.1002/chem.202100110}},
  volume       = {{27}},
  year         = {{2021}},
}