Microbial platforms and tools for benzylisoquinoline alkaloid biosynthesis

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This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports work to develop novel engineering approaches for natural product synthesis. The engineering of biosynthetic pathways in microbial hosts represents a newer approach to chemical synthesis with exciting potential. While traditional approaches to engineering cellular biosynthesis processes require a significant investment of time and resources that does not scale with the complexity represented in many natural product biosynthesis schemes, recent advances in synthetic biology are transforming the complexity of genetic networks that can be engineered in biological systems. The goal of this research is to develop a microbial biosynthesis platform for an important class of natural products, the benzylisoquinoline alkaloids (BIAs). The investigators will utilize this microbial platform to broadly advance scalable biosynthesis strategies for complex natural products and provide insights into nature's own biosynthetic strategies. Specifically, the investigators propose to: (i) construct synthetic pathways for the biosynthesis of early BIAs from amino acid precursors; (ii) develop insulation strategies for the synthetic BIA pathway through modification of native yeast pathways; (iii) develop strategies for organelle routing for biosynthesis specialization and compartmentalization; (iv) link optimized BIA branches for the total synthesis of specialty BIAs; (v) develop new biological engineering curriculum that emphasizes foundational concepts in synthetic biology and integrated systems design strategies.