• Protein engineering and in sil...

*Result*: Protein engineering and in silico approaches to enhance bacterial lactase activity: A global perspective.

Title:
Protein engineering and in silico approaches to enhance bacterial lactase activity: A global perspective.
Authors:
Sánchez-Torres P; Food Biotechnology Department, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Agroquímica y Tecnología de Alimentos (IATA), Catedrático Agustín Escardino Benlloch 7, Paterna, Valencia, 46980, Spain., Torrat-Noves JC; Food Biotechnology Department, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Agroquímica y Tecnología de Alimentos (IATA), Catedrático Agustín Escardino Benlloch 7, Paterna, Valencia, 46980, Spain., Valera-García E; Food Biotechnology Department, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Agroquímica y Tecnología de Alimentos (IATA), Catedrático Agustín Escardino Benlloch 7, Paterna, Valencia, 46980, Spain., Talens-Perales D; Food Biotechnology Department, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Agroquímica y Tecnología de Alimentos (IATA), Catedrático Agustín Escardino Benlloch 7, Paterna, Valencia, 46980, Spain. Electronic address: d.talens@iata.csic.es.
Source:
International journal of biological macromolecules [Int J Biol Macromol] 2026 Feb; Vol. 341 (Pt 1), pp. 150141. Date of Electronic Publication: 2026 Jan 08.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
Imprint Name(s):
Publication: Amsterdam : Elsevier
Original Publication: Guildford, Eng., IPC Science and Technology Press.
MeSH Terms:
Lactase*/genetics , Lactase*/chemistry , Lactase*/metabolism , Protein Engineering*/methods , Computer Simulation* , Bacterial Proteins*/genetics , Bacterial Proteins*/chemistry , Bacterial Proteins*/metabolism , Bacteria*/enzymology , Bacteria*/genetics, Phylogeny ; Computational Biology ; Models, Molecular ; Amino Acid Sequence
Substance Nomenclature:
EC 3.2.1.108 (Lactase)
0 (Bacterial Proteins)
Entry Date(s):
Date Created: 20260110 Date Completed: 20260123 Latest Revision: 20260123
Update Code:
20260130
DOI:
10.1016/j.ijbiomac.2026.150141
PMID:
41519330
Database:
MEDLINE

*Further Information*

*This study explores several strategies to develop new lactases with enhanced properties: (1) modification of TmLacS, (2) random mutagenesis, and (3) in-silico approaches for the discovery of novel lactases. Initial efforts focused on introducing a loop into TmLacS, a heat-resistant lactase, resulting in the TmLacS_SL variant, which exhibited a marked reduction in its maximum catalytic rate. Random shuffling mutagenesis was then applied to generate variants of both TmLacS and TmLacS_SL. This approach yielded more active enzymes: the TmLacS mutant TmLac_3H6 displayed a significant increase in total activity, while the TmLacS_SL mutant TmLacS_SL_3A11 showed up to a fivefold improvement compared to TmLacS_SL. In parallel, an in-silico strategy was employed to identify novel β-galactosidases with potential lactase activity. This included bioinformatics screening, phylogenetic analysis to refine the candidate list, and the selection of sequences from thermoresistant organisms with similarities to the desired β-galactosidases. Through this process, the initial pool of over 100 sequences was narrowed to four promising proteins: ThStLac, PsTheLac, CalHydLac, and TeLac. Further characterization revealed TeLac as the most efficient enzyme.
(Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)*

*Declaration of competing interest The authors declare no competing financial interest.*