Purification of active recombinant human histone deacetylase 1 (HDAC1) overexpressed in Escherichia coli

Biotechnol Lett. 2018 Oct;40(9-10):1355-1363. doi: 10.1007/s10529-018-2585-5. Epub 2018 Jun 14.

Abstract

Objective: We attempted to overexpress Human Histone Deacetylase 1 (HDAC1) in Escherichia coli.

Results: A synthetic gene coding for HDAC1, and optimised for E. coli codon usage, was cloned into pBADHisB, generating pBAD-rHDAC1. This construct was used to transform E. coli TOP10, and the target protein was overexpressed and partially purified. According to its elution volume from a Superdex 200 column, the partially purified rHDAC1 was obtained in aggregated form, i.e., as an octamer. The dissociation of octameric HDAC1 was tested using several agents, among which sodium dodecyl sulfate was competent in partially dissociating rHDAC1 aggregates. When the enzyme activity was tested in vitro using 3H-acetyl-labelled histones both protein samples, aggregated and dissociated, were active. Hence, our results suggest that E. coli represents an alternative system for the production of the recombinant HDAC1.

Conclusions: We described a procedure for the overexpression in E. coli of recombinant HDAC1, the purification of which in active form can be successfully performed, although yielding an octameric aggregate.

Keywords: Escherichia coli; Heterologous expression; Human histone deacetylase 1 (HDAC1); Protein dissociation; Protein purification.

MeSH terms

  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 1 / isolation & purification*
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Protein Engineering / methods*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification*
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • HDAC1 protein, human
  • Histone Deacetylase 1