Novel Biocatalytic Structures for Sustainable Synthesis of Fine Chemicals and Biologically Active Substances

Suny College Of Environmental Science And Forestry, Syracuse NY

Investigators

Abstract

0853454 Gitsov, Ivan Biocatalysis plays a very important role in numerous natural and technological processes. One of the major deficiencies of many native enzymes, however, is their inability to transform water-insoluble substrates, which often necessitates the use of harsh reaction conditions and polluting technologies based on toxic organic and inorganic catalysts, solvents and their mixtures. The main objective of this proposal is to develop a family of new highly efficient, recyclable and environmentally benign biocatalytic structures for the synthesis of hydrophobic substrates of biological, pharmaceutical or biotechnological importance, and test the ability of these nanodevices to facilitate biotransformations in water and at ambient temperature. The novelty in the design of these nano-constructs is that individual or multiple glycoproteins will be positioned in the core of a micelle or supramolecular hydrogel, constructed of linear-dendritic copolymers. This macromolecular architectural principle is clearly distinguishable from previous and current research on dendrimer- and polymer-supported enzymes. In this project the dendritic fragments do not serve as crosslinking agents and are not covalently attached to the enzymes. They bind the glycoproteins by soft regioselective nanocontacts. Thus these perfectly branched fragments will serve not only as supports of the enzymatic functions, but will also act as a cooperative micro-environment to provide transition state stabilization, enhancement of enzymatic activity, and selectively promote the uptake and internal transport of substrates and release of products. This protective nanoporous shell will also facilitate the recovery and recycling of the enzymatic assemblies by simple filtration or centrifugation. Three specific aims will be pursued to produce the targeted biocatalysts and demonstrate their advantages and applicability for sustained, "green" chemistry processes: 1) Construct series of recyclable linear-dendritic enzyme complexes in micellar- or physical hydrogel form without chemical bond formation and explore the influence of chemical, structural and environmental factors on the mechanism and kinetics of the catalyzed reactions; 2) Test single-enzyme constructs with the highest catalytic activity in selected tandem processes, which will involve formation of novel biologically active dimers, oligomers and polymers for multi-purpose applications; 3) Evaluate single- and dual-enzyme complexes for "green chemistry" cascade reactions, where the products, formed in the dendritic shell or through the first enzyme will serve as exclusive substrates of the second enzyme. The project will integrate in a unique way elements from the kinetics of enzymatic biocatalysis and fundamental self-assembly processes with the synthesis of chemically functional organic and polymeric materials. The impact of this research will result in the development of novel environmentally friendly synthetic strategies for important fine chemicals and pharmaceutical intermediates using water, low energy consumption and renewable natural resources. Broader impacts of the proposed activities will be manifested by the creation of new procedures for in situ drug synthesis and delivery using unique biocompatible nanodevices. The proposed work will also pave the way to a better understanding of vital natural biosynthetic processes involving multiple enzymes. The investigations in this project also provide excellent educational and training opportunities for undergraduate and graduate students in a truly interdisciplinary research at the intersection of polymer materials and supramolecular chemistry, biotechnology and enzymatic catalysis, organic synthesis and macromolecular nanoscience.