Metabolic engineering of Saccharomyces cerevisiae for alkaloid production

Abstract

Natural products or natural‐product inspired molecules comprise most successful drugs. However, these high‐value molecules are difficult to synthesize chemically and are often isolated through inefficient extractions from natural sources. As such, they are increasingly targeted for production by biosynthesis from engineered microorganisms. The budding yeast species Saccharomyces cerevisiae has proven to be a powerful microorganism for heterologous expression of biosynthetic pathways. Yet many challenges are currently faced in engineering yeast strains for the biosynthesis of complex secondary metabolite production. Synthetic biology is advancing the development of new tools for constructing, controlling, and optimizing complex metabolic pathways in yeast.I will describe recent work in engineering yeast as a production host for diverse alkaloid compounds, and in particular the benzylisoquinoline alkaloids (BIAs). Yeast strains engineered to express enzymes from diverse organisms, including plants, bacteria, and humans, have been demonstrated to synthesize numerous intermediates and end‐products in this biosynthetic pathway. In addition, I will describe the development of synthetic biology platforms that are providing new approaches to optimizing complex biosynthetic pathways.