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

Abstract

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.

Keywords: HDAC inhibitors; Histone acetylation; Hydroxamic acids; Lipocalin-type prostaglandin D2 synthase; Molecular modelling; Nicotiana tabacum BY-2 cells; Organic synthesis; Recombinant protein.