Light-based control of metabolic flux through assembly of synthetic organelles.

TitleLight-based control of metabolic flux through assembly of synthetic organelles.
Publication TypeJournal Article
Year of Publication2019
AuthorsZhao, EM, Suek, N, Wilson, MZ, Dine, E, Pannucci, NL, Gitai, Z, Avalos, JL, Toettcher, JE
JournalNat Chem Biol
Volume15
Issue6
Pagination589-597
Date Published2019 06
ISSN1552-4469
KeywordsIndoles, 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>

DOI10.1038/s41589-019-0284-8
Alternate JournalNat. Chem. Biol.
PubMed ID31086330
PubMed Central IDPMC6755918
Grant ListDP1 AI124669 / AI / NIAID NIH HHS / United States
DP2 EB024247 / EB / NIBIB NIH HHS / United States