Metabolic engineering and in vitro biosynthesis of phytochemicals and non-natural analogues

• Published in: Plant science (Limerick) 2013-09, Vol.210, p.10-24
• Main Authors: Mora-Pale, Mauricio, Sanchez-Rodriguez, Sandra P., Linhardt, Robert J., Dordick, Jonathan S., Koffas, Mattheos A.G.
• Format: Article
• Language: English
• Subjects: Alkaloids; Alkaloids - chemistry; Alkaloids - metabolism; bioavailability; biochemical pathways; Biological Products - chemistry; Biological Products - metabolism; biosynthesis; cells; chemical structure; chronic diseases; Escherichia coli - genetics; Escherichia coli - metabolism; Flavonoids; Flavonoids - metabolism; Gene Expression; genes; isoprenoids; Metabolic Engineering; Metabolic Networks and Pathways; metabolites; microorganisms; Phytochemicals; Phytochemicals - chemistry; Phytochemicals - metabolism; Plant Cells - chemistry; Plant Cells - metabolism; Plants - chemistry; Plants - genetics; Plants - metabolism; Recombinant microogranisms; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; solvents; stilbenes; Stilbenes - chemistry; Stilbenes - metabolism; Synthetic Biology; Terpenes - chemistry; Terpenes - metabolism; Terpenoids; toxicity
• ISSN: 0168-9452; 1873-2259
• DOI: 10.1016/j.plantsci.2013.05.005

•Optimization and reconstruction in vivo of natural compounds.•Diversification of natural and non-natural compounds in plant cells.•In vitro diversification of natural and non-natural compounds by terpenoid synthases and tailoring enzymes.•Diversification of non-natural products combining metabolic engineering and in vitro biocatalysis. Over the years, natural products from plants and their non-natural derivatives have shown to be active against different types of chronic diseases. However, isolation of such natural products can be limited due to their low bioavailability, and environmental restrictions. To address these issues, in vivo and in vitro reconstruction of plant metabolic pathways and the metabolic engineering of microbes and plants have been used to generate libraries of compounds. Significant advances have been made through metabolic engineering of microbes and plant cells to generate a variety of compounds (e.g. isoprenoids, flavonoids, or stilbenes) using a diverse array of methods to optimize these processes (e.g. host selection, operational variables, precursor selection, gene modifications). These approaches have been used also to generate non-natural analogues with different bioactivities. In vitro biosynthesis allows the synthesis of intermediates as well as final products avoiding post-translational limitations. Moreover, this strategy allows the use of substrates and the production of metabolites that could be toxic for cells, or expand the biosynthesis into non-conventional media (e.g. organic solvents, supercritical fluids). A perspective is also provided on the challenges for generating novel chemical structures and the potential of combining metabolic engineering and in vitro biocatalysis to produce metabolites with more potent biological activities.