Synthesis and biological effects of small molecule enhancers for improved recombinant protein production in plant cell cultures.

Autor: Rebelo BA; Plant Cell Biology Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal; Bioorganic Chemistry Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal., Santos RB; Plant Cell Biology Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal., Ascenso OS; Bioorganic Chemistry Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal., Nogueira AC; Plant Cell Biology Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal., Lousa D; Protein Modelling Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal., Abranches R; Plant Cell Biology Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal. Electronic address: ritaa@itqb.unl.pt., Ventura MR; Bioorganic Chemistry Laboratory, Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal. Electronic address: rventura@itqb.unl.pt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Jan; Vol. 94, pp. 103452. Date of Electronic Publication: 2019 Nov 26.
DOI: 10.1016/j.bioorg.2019.103452
Abstrakt: Histone deacetylases are involved in chromatin remodelling and thus play a vital role in the epigenetic regulation of gene expression. HDAC inhibitors alter the acetylation status of histone and non-histone proteins to regulate various cellular events such as transcription. Novel HDAC inhibitors were designed and synthesised to promote higher levels of recombinant protein production in tobacco cell cultures. The effect of these chemical enhancers on the epigenetic profiles in plant cells has been evaluated by molecular docking, in vitro and in vivo studies. The addition of these novel enhancers led to an increase in histone H3 acetylation levels that promoted an increase in the accumulation levels of the recombinant protein in cell culture. These results can pave the way for the application of these enhancers to improve the production of high value products in plant cell based systems.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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