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Plant Physiol Biochem. 2017 Sep;118:130-137. doi: 10.1016/j.plaphy.2017.06.013. Epub 2017 Jun 13.

Biotechnological production of recombinant tissue plasminogen activator protein (reteplase) from transplastomic tobacco cell cultures.

Author information

1
Laboratori de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn, 08028 Barcelona, Spain.
2
Department of Biotechnology, Institute of Science, High Technology and Environmental Science, Graduate University of Advanced Tecnology, P.O. Box 76315-117, Kerman, Iran.
3
Department of Plant Breeding, Faculty of Agriculture, Tarbiat Modares University, P.O. Box 14115-336, Tehran, Iran.
4
Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain.
5
Department of Botany and Plant Physiology, Campus Miguel de Unamuno, University of Salamanca, E-37007, Salamanca, Spain.
6
Laboratori de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn, 08028 Barcelona, Spain. Electronic address: javierpalazon@ub.edu.

Abstract

Transplastomic plants are a system of choice for the mass production of biopharmaceuticals due to the polyploidy of the plastid genome and the low risk of pollen-mediated outcrossing because of maternal inheritance. However, as field-grown plants, they can suffer contamination by agrochemicals and fertilizers, as well as fluctuations in yield due to climatic changes and infections. Tissue-type plasminogen activator (tPA), a protein used to treat heart attacks, converts plasminogen into plasmine, which digests fibrin and induces the dissolution of fibrin clots. Recently, we obtained transplastomic tobacco plants carrying the K2S gene encoding truncated human tPA (reteplase) with improved biological activity, and confirmed the presence of the target protein in the transgenic plant leaves. Considering the advantages of plant cell cultures for biopharmaceutical production, we established a cell line derived from the K2S tobacco plants. The active form of reteplase was quantified in cultures grown in light or darkness, with production 3-fold higher in light.

KEYWORDS:

Human tissue plasminogen activator (tPA); Reteplase; Tobacco cell cultures; Transplastomic plants

PMID:
28633085
DOI:
10.1016/j.plaphy.2017.06.013
[Indexed for MEDLINE]

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