Compatible solutes constitute a structurally diverse class of small molecules that are synthesized by microorganisms and different cell types to protect themselves against the effects of various exogenous stresses. They are often referred to as osmolytes because one of their main roles in cellular physiology is to counteract high external concentrations of salt or sugars. Organisms dwelling at environmental extremes of temperature, pH or salt are particularly rich in compatible solutes and produce a range of compounds that appear to be unique to the lifestyle under extremophilic conditions. Many of these so-called "extremolytes" have a glycosidic structure as in glucosylglycerol or mannosylglycerate, for example. Typically, they are composed of a sugar residue linked to an aglycon that is often derived from glycerol but varies in the final structure. Several studies have indicated that these natural glycosides show an outstanding capability of protecting cells or macromolecular constituents thereof against denaturation. Various technological applications are immediately implied by these findings. The glycosides could be used as stabilizers of biopharmaceuticals during downstream processing and formulation, for the conservation of cells and tissues, and as skin-care reagents and moisturizers in cosmetic products. Despite the clear potential for commercialization, there are currently no high-yielding and technologically mature processes for the production of compatible solutes of the glycoside type. Chemical synthesis of compounds having exactly the structure found in nature is laborious and therefore expensive. The capacity of the biosynthetic pathway is usually too low for technological exploitation. This project therefore proposes the use of biocatalysis. The extremely efficient transglycosylation catalyzed by wild-type and engineered forms of sucrose phosphorylase, as already proven in the enzymatic synthesis of alpha-glucosyl glycerol, will be exploited for the synthesis of the three most prevalent glycosides known to function as compatible solutes: alpha-glucosyl glycerate; alpha-mannosyl glycerate; alphamannosyl glyceramide. The enzyme will further offer the possibility to chemically diversify the natural glycosides into structurally similar compounds that may have different and improved properties. Structure-guided protein engineering combined with directed evolution of sucrose phosphorylase will be used to obtain catalysts that are optimized for the particular tasks in synthesis.
|Effective start/end date||1/04/09 → 28/02/12|
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.