In nature, enzymes that catalyze sequential reactions are often assembled as clusters or complexes. The formation of multienzyme complexes, or metabolons, brings the enzyme active sites into proximity to promote intermediate transfer, decrease intermediate leakage, and streamline the metabolic flux towards the desired products. We and others have developed synthetic versions of metabolons through various strategies to enhance the catalytic rates for synthesizing valuable chemicals inside microbes. Synthetic multienzyme complexes range from static enzyme nanostructures to dynamic enzyme coacervates. Enzyme complexation optimizes the metabolic fluxes inside microbes, increases the product titer, and supplies the field with high-yield microbe strains that are amenable to large-scale fermentation. Enzyme complexes constructed inside microbial cells can be separated as independent entities and catalyze biosynthetic reactions ex vivo; such a feature gains these complexes another name, "synthetic organelles" -new subcellular entities with independent structures and functions. Still, the field is seeking new strategies to better balance dynamicity and confinement and to achieve finer control of local compartmentalization in the cells, as the natural multienzyme complexes do. Industrial applications of synthetic multienzyme complexes for the large-scale production of valuable chemicals are yet to be realized. This review focuses on synthetic multienzyme complexes that are constructed and function inside microbial cells.
Abstract:The isoquinoline motif and its derivatives are of significant interest due to their important biological activities. The effective synthesis of substituted isoquinoline compounds has historically been a significant challenge. A new palladium-catalyzed C-H activation/annulation of N-methoxy benzamides and 2,3-allenoic acid esters is described. For the first time, 2,3-allenoic acid esters are employed for the syntheses of 3,4-substituted hydroisoquinolones, the heteroannulation of allenes proceeded smoothly and afforded the products with good yields and excellent regioselectivity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.