Production of bioactive plant secondary metabolites through in vitro technologies-status and outlook

Abstract

Medicinal plants have been used by mankind since ancient times, and many bioactive plant secondary metabolites are applied nowadays both directly as drugs, and as raw materials for semi-synthetic modifications. However, the structural complexity often thwarts cost-efficient chemical synthesis, and the usually low content in the native plant necessitates the processing of large amounts of field-cultivated raw material. The biotechnological manufacturing of such compounds offers a number of advantages like predictable, stable, and year-round sustainable production, scalability, and easier extraction and purification. Plant cell and tissue culture represents one possible alternative to the extraction of phytochemicals from plant material. Although a broad commercialization of such processes has not yet occurred, ongoing research indicates that plant in vitro systems such as cell suspension cultures, organ cultures, and transgenic hairy roots hold a promising potential as sources for bioactive compounds. Progress in the areas of biosynthetic pathway elucidation and genetic manipulation has expanded the possibilities to utilize plant metabolic engineering and heterologous production in microorganisms. This review aims to summarize recent advances in the in vitro production of high-value plant secondary metabolites of medicinal importance.Key points• Bioactive plant secondary metabolites are important for current and future use in medicine• In vitro production is a sustainable alternative to extraction from plants or costly chemical synthesis• Current research addresses plant cell and tissue culture, metabolic engineering, and heterologous production.

Keywords: Cell suspension; Hairy roots; Heterologous production; Plant secondary metabolites; Plant tissue culture.

Fig. 1

Chemical structures of some bioactive plant secondary metabolites used in medicine

Fig. 2

Methods for the production of bioactive secondary metabolites through plant in vitro culture. A Establishment of in vitro cultures after surface sterilization of plant material. Callus formation can also be induced on material from organ cultures. Reversely, organs like roots or shoots can be regenerated from callus. Hairy roots are obtained by infection of sterilized donor plant, or in vitro cultivated material, with Agrobacterium rhizogenes. B Multiplication of primary callus/organs/roots, first selection, and establishment of liquid cultures. C Selection of high yielding lines and optimization of culture conditions (nutrient medium composition, inoculum density, temperature, light, agitation and aeration). Strategies like elicitation, precursor feeding, or immobilization are pursued to further improve productivity. D The bioreactor design will depend on the culture type: stirred tanks, but also airlift and bubble column reactors for cell suspensions; mist or spray reactors and temporary immersion systems for organ cultures (including hairy roots)