The construction of stimulus-responsive supramolecular complexes of metabolic pathway enzymes, inspired by natural multi-enzyme assemblies (metabolons), provides an attractive avenue for efficient and spatio-temporally controllable one-pot biotransformations. Rutgers chemists Lu Yang, Elliott Dolan, Sophia Tan and Sagar Khare (sagardkharelab.org) and mathematicians Jason Lin and Eduardo Sontag constructed a phosphorylation- and optically-responsive metabolon for the biodegradation of the environmental pollutant 1,2,3-trichloropropane (TCP). In results described in the journal ChemBioChem, the researchers fused three enzymes in the TCP degradation pathway to variants of either peptide-binding domains (one of which was computationally designed to incorporate an unnatural photocrosslinkable amino acid) or their corresponding binding peptides, and enzyme co-localization in response to phosphorylation and UV-light was demonstrated. Metabolon formation led to an increase in pathway efficiency, and because the developed method is modular and generalizable, it should enable spatio-temporal control over formation and functioning of a wide variety of synthetic biotransformations.
The figure shows A) synthetic pathway for the biodegradation of 1,2,3-trichloropropane B) the schematic of the designed multi-enzyme assembly controlled by both phosphorylation and UV light and C) three-component assembly had the highest conversion efficiency.
Published Online: August 10, 2017
More Information: http://onlinelibrary.wiley.com/doi/10.1002/cbic.201700425/abstract
Year of Research Highlight: 2017