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 productionGraphical abstract
Highlights
Mankind has been using medicinal plants since thousands of years (Fabricant and Farnsworth 2001; Kinghorn et al 2011), and herbal medicines continue to be used around the world, but not solely, in developing countries (Robinson and Zhang 2011)
Notwithstanding the fact that high yielding cell suspension and organ lines can be established for a variety of plants, plant tissue cultures suffer from a number of disadvantages that limit the large-scale commercial application to but a few processes
Geranyl diphosphate and olivetolic acid are initial precursors which are condensed to cannabigerolic acid (CBGA). This intermediate is further converted to cannabidiolic acid (CBDA), Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and cannabichromenic acid (CBCA) (Flores-Sanchez and Verpoorte 2008). In their attempts to establish a platform for the heterologous production of cannabinoids in yeasts, Zirpel et al (2015) initially showed that Pichia pastoris expressing Δ9-THCA synthase from C. sativa produced Δ9-THCA from CBGA in a whole cell bioconversion assay
Summary
Mankind has been using medicinal plants since thousands of years (Fabricant and Farnsworth 2001; Kinghorn et al 2011), and herbal medicines continue to be used around the world, but not solely, in developing countries (Robinson and Zhang 2011). Isolation of morphine from the opium poppy Papaver somniferum by Sertürner some 200 years ago (Klockgether-Radke 2002), and the subsequent isolation of compounds like, e.g., cocaine or digitoxine, marked the beginning of rational drug discovery (Pferschy-Wenzig and Bauer 2015), as plant-derived drugs could be administered much more precisely compared to the crude herbal extracts (Li and Vederas 2009). A number of recent reviews deals with plant tissue culture for the production of secondary compounds, for example by Chandran et al (2020), Gutierrez-Valdes et al (2020), Marchev et al (2020), Cardoso et al (2019), Kreis (2019), Rahmat and Kang (2019), and more. The present minireview on the one hand highlights recent achievements in the production of medically important plant secondary metabolites using various in vitro technologies, including most recent approaches like metabolic engineering and heterologous production in microorganisms. Progress in the optimization of in vitro productivity will be analyzed on the basis of selected compounds
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