Applied Microbiology and Biotechnology

, Volume 100, Issue 23, pp 9933–9941 | Cite as

Histone-dependent IgG conservation in octanoic acid precipitation and its mechanism

  • Quan Chen
  • Phyllicia Toh
  • Yue Sun
  • Sarah Maria Abdul Latiff
  • Aina Hoi
  • Mo Xian
  • Haibo Zhang
  • Rui NianEmail author
  • Wei ZhangEmail author
  • Pete Gagnon
Biotechnological products and process engineering


Octanoic acid (OA) precipitation has long been used in protein purification. Recently, we reported a new cell culture clarification method for immunoglobulin G (IgG) purification, employing an advance elimination of chromatin heteroaggregates with a hybrid OA-solid phase system. This treatment reduced DNA more than 3 logs, histone below the detection limit (LOD), and non-histone host cell proteins (nh-HCP) by 90 % while conserving more than 90 % of the IgG monomer. In this study, we further investigated the conservation of IgG monomer and antibody light chain (LC) to the addition of OA/OA-solid phase complex, with or without histone and DNA in different combinations. The results showed that highly basic histone protein was the prime target in OA/OA-solid phase precipitation system for IgG purification, and the selective conservation of IgG monomer in this system was histone dependent. Our findings partially support the idea that OA works by sticking to electropositive hydrophobic domains on proteins, reducing their solubility, and causing them to agglomerate into large particles that precipitate from solution. Our findings also provide a new perspective for IgG purification and emphasize the necessity to re-examine the roles of various host contaminants in IgG purification.


Octanoic acid Agglomeration Histone IgG Light chain 



This work was financially supported by QIBEBT (Qingdao Institute of Bioenergy and Bioprocess Technology) Start-up Fund (No. Y571061905) and also by the Biomedical Research Council of A*STAR and Exploit Technologies Pte Ltd., of Singapore (No. ETPL/12-R15GAP-0009).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoChina
  2. 2.Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR)SingaporeSingapore

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