Title | Light-based control of metabolic flux through assembly of synthetic organelles. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Zhao, EM, Suek, N, Wilson, MZ, Dine, E, Pannucci, NL, Gitai, Z, Avalos, JL, Toettcher, JE |
Journal | Nat Chem Biol |
Volume | 15 |
Issue | 6 |
Pagination | 589-597 |
Date Published | 2019 Jun |
ISSN | 1552-4469 |
Keywords | Indoles, Light, Metabolic Engineering, Metabolic Networks and Pathways, Optogenetics, Organelles, Saccharomyces cerevisiae, Synechocystis, Synthetic Biology |
Abstract | <p>To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems compartmentalize enzymes into organelles or post-translationally induce activity under certain conditions. Here we report that optogenetic control can be used to extend compartmentalization and dynamic control to engineered metabolisms in yeast. We describe a suite of optogenetic tools to trigger assembly and disassembly of metabolically active enzyme clusters. Using the deoxyviolacein biosynthesis pathway as a model system, we find that light-switchable clustering can enhance product formation six-fold and product specificity 18-fold by decreasing the concentration of intermediate metabolites and reducing flux through competing pathways. Inducible compartmentalization of enzymes into synthetic organelles can thus be used to control engineered metabolic pathways, limit intermediates and favor the formation of desired products.</p> |
DOI | 10.1038/s41589-019-0284-8 |
Alternate Journal | Nat Chem Biol |
PubMed ID | 31086330 |
PubMed Central ID | PMC6755918 |
Grant List | DP1 AI124669 / AI / NIAID NIH HHS / United States DP2 EB024247 / EB / NIBIB NIH HHS / United States |