Application of metabolic engineering to enhance the content of alkaloids in medicinal plants

• Published in: Metabolic engineering communications Vol. 14; p. e00194
• Main Authors: Mora-Vásquez, Soledad, Wells-Abascal, Guillermo Gael, Espinosa-Leal, Claudia, Cardineau, Guy A., García-Lara, Silverio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2022; Elsevier
• Subjects: Applied biotechnology; biosynthesis; enzymes; Gene editing; Gene overexpression; Plant transformation; Review; Secondary metabolites; transcription factors; Gene overexpression; Secondary metabolites; Plant transformation; Applied biotechnology; Gene editing
• ISSN: 2214-0301; 2214-0301
• DOI: 10.1016/j.mec.2022.e00194

Plants are a rich source of bioactive compounds, many of which have been exploited for cosmetic, nutritional, and medicinal purposes. Through the characterization of metabolic pathways, as well as the mechanisms responsible for the accumulation of secondary metabolites, researchers have been able to increase the production of bioactive compounds in different plant species for research and commercial applications. The intent of the current review is to describe the metabolic engineering methods that have been used to transform in vitro or field-grown medicinal plants over the last decade and to identify the most effective approaches to increase the production of alkaloids. The articles summarized were categorized into six groups: endogenous enzyme overexpression, foreign enzyme overexpression, transcription factor overexpression, gene silencing, genome editing, and co-overexpression. We conclude that, because of the complex and multi-step nature of biosynthetic pathways, the approach that has been most commonly used to increase the biosynthesis of alkaloids, and the most effective in terms of fold increase, is the co-overexpression of two or more rate-limiting enzymes followed by the manipulation of regulatory genes. •The content of highly demanded alkaloids is very low in plants.•Metabolic engineering has enabled higher accumulation of alkaloids in plants.•Co-overexpression of key enzymes and regulators greatly increases alkaloid content.•CRISPR technology is a promising tool to increase the content of alkaloids.