Site-Directed Mutagenesis of Two-Domain Laccase ScaSL for Obtaining a Biocatalyst with Improved Characteristics

Направленная мутагенез двухдоменной лакказы ScaSL для получения биокатализатора с улучшенными характеристиками
Svetlana Tishchenko, Azat Gabdulkhakov, Liubov I. Trubitsina, Ivan V. Trubitsin, Azat Abdullatypov, Аnna A. Larionova, Marina Petrakova, V. E. Trubitsyn, K. Egorov, A. A. Leontievsky, С. В. Алферов, О. Н. Понаморева
2024-10-05

H286A H286T H286W F232Y/F233Y mutantsdirect electron transfer (DET) with MWCNT-modified electrodesredox potential changes (0.45 V, 0.51 V)site-directed mutagenesistwo-domain laccase ScaSL
Analysis of the structure of two-domain laccase ScaSL from Streptomyces carpinensis VKM Ac-1300 (with a middle-redox potential) revealed determinants that could affect the increased potential of ScaSL. Site-directed mutagenesis of the ScaSL laccase was carried out, and mutants H286A, H286T, H286W, and F232Y/F233Y were obtained. Replacement of His 286 with Ala led to a decrease in redox potential (0.45 V) and an increase in stability at pH 9 and 11; replacement with Thr led to an increase in redox potential (0.51 V) but to a decrease in the thermal stability of the protein; replacement with Trp did not affect the enzyme properties. Replacement of Phe residues 232 and 233 with Tyr led to a shift in enzyme activity to the acidic pH range without changing the redox potential and a decrease in the thermostability and pH stability of the enzyme. All mutants more efficiently oxidized phenolic substrate 2,6-DMP and were able to participate in direct electron transfer (DET) with MWCNT-modified electrodes. The F232Y/F233/Y mutant was unable to degrade triphenylmethane dyes without a mediator but showed a greater degree of decolorization of azo dyes in the presence of the mediator. The crystal structure of laccase with the highest potential was determined with high resolution.
1
All mutants showed improved oxidation of the phenolic substrate 2,6-DMP and were capable of direct electron transfer with MWCNT-modified electrodes.
2
F232Y/F233Y double mutation shifted enzyme activity toward acidic pH without changing redox potential and decreased thermostability and pH stability.
3
F232Y/F233Y mutant could not degrade triphenylmethane dyes without a mediator but achieved greater decolorization of azo dyes in the presence of a mediator.
4
H286A mutation decreased redox potential to 0.45 V and increased stability at pH 9 and 11.
5
H286T mutation increased redox potential to 0.51 V but decreased thermal stability.
6
H286W mutation did not affect measured enzyme properties compared to wild type.
7
Site-directed mutagenesis of two-domain laccase ScaSL produced mutants H286A, H286T, H286W, and F232Y/F233Y with distinct biochemical effects.
8
The crystal structure of the laccase variant with the highest redox potential was determined at high resolution.

Two-domain laccase ScaSL from Streptomyces carpinensis VKM Ac-1300 (wild-type and site-directed mutants H286A, H286T, H286W, and F232Y/F233Y)

Effects of site-directed mutations on enzyme properties: redox potential, pH and thermal stability, substrate specificity and activity (oxidation of 2,6-DMP and dye decolorization), and ability to perform direct electron transfer on MWCNT-modified electrodes; structural basis (crystal structure) of altered potential

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2024-10-05
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Authors
Svetlana Tishchenko
Azat Gabdulkhakov
Liubov I. Trubitsina
Ivan V. Trubitsin
Azat Abdullatypov
Аnna A. Larionova
Marina Petrakova
V. E. Trubitsyn
K. Egorov
A. A. Leontievsky
С. В. Алферов
О. Н. Понаморева
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