Team:Virginia

Manifold

Through the use of Bacterial Microcompartments and DNA Scaffolds,
We're revolutionizing biosynthesis with intracellular nanoreactors.
Find out more in our project description >
Abstract
The lack of a versatile and reliable way to improve
metabolic flux Metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activity under different conditions.
channeling, pathway
orthogonalityThe growth-independant optimization of a pathway,for the production of a target chemical. These pathways are characterized by the minimization of interactions between the chemical-producing pathways and the biomass-producing pathways. Physiologically, this means in perfect orthogonal networks,the product pathway shares no enzymatic steps with cellular pathways that are responsible for the production of precursors required for biomass and, only a single metabolite serves as a branch point from which product and biomass pathways diverge.
, and product yields is a major impediment to the expanded utilization of biosynthesis for the production of drugs and industrially valuable chemicals. Manifold, a platform technology that addresses this problem, consists of
bacterial microcompartmentsBacterial microcompartments (BMCs) are organelle-like structures, consisting of a protein shell that encloses enzymes and other proteins. BMCs are typically about 40-200 nanometers in diameter and are entirely made of proteins. The shell functions like a membrane, as it is selectively permeable.
(BMCs) with encapsulated
dsDNA scaffold Non-coding linear DNA containing repetitive sequence specific regions for zinc-finger protein-domain ligation. This work is used in DNA origami to assemble precise nanoscale structures with custom geometries and fully addressable surfaces.
that sequester and spatially organize, at fixed concentrations, biosynthetic enzymes presented as
zinc-finger fusion proteinsA zinc finger is a small, functional, independently folded domain that coordinates one or more zinc ions to stabilize its structure through cysteine and/or histidine residues. Zinc fingers are structurally diverse and exhibit a wide range of functions, from DNA- or RNA-binding to protein-protein interactions and membrane association
. Here we deliver the designs for an E. coli cell capable of synthesizing resveratrol using the Manifold platform. The Manifold platform will help lower costs and expand the applications of chemical biosynthesis.