Production of the cyanogenic glycoside dhurrin in yeast

• Published in: Metabolic engineering communications Vol. 9; p. e00092
• Main Authors: Kotopka, Benjamin J., Smolke, Christina D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2019; Elsevier
• Subjects: biosynthesis; Biosynthetic gene cluster; crops; Cyanogenic glycoside; cyanogenic glycosides; Dhurrin; enzymes; genetic engineering; heterologous gene expression; multigene family; Plant natural product; Saccharomyces cerevisiae; tyrosine; yeasts; Dhurrin; Plant natural product; Biosynthetic gene cluster; Saccharomyces cerevisiae; Cyanogenic glycoside
• ISSN: 2214-0301; 2214-0301
• DOI: 10.1016/j.mec.2019.e00092

Cyanogenic glycosides are defense compounds found in a wide range of plant species, including many crops. We demonstrate that the cyanogenic glucoside dhurrin, naturally found in sorghum, can be produced at high titers in Saccharomyces cerevisiae, constituting the first report of cyanogenic glycoside production in a microbe. Genetic modifications to increase the supply of the dhurrin precursor tyrosine enabled dhurrin production in excess of 80 mg/L. The dhurrin-producing yeast strain was used as a chassis to investigate previously uncharacterized enzymes identified close to the biosynthetic gene cluster containing the dhurrin pathway enzymes. This work shows the potential of heterologous expression in yeast to facilitate investigations of plant cyanogenic glycoside pathways. •First production of cyanogenic glycosides in a microbe.•Strategies for optimizing production of cyanogenic glycosides.•Platform for rapidly characterizing the enzymes which constitute cyanogenic glycoside biosynthetic pathways.