Project: Metabolic and Enzyme Engineering for the Biotechnological Production of Partially Acetylated Chitosans
Just as people have to communicate to build a community and, eventually, a society, cells need to communicate to build a tissue and, eventually, an organism. Cells have evolved a sophisticated molecular language, and complex sugar molecules form key words of this language. One example are sugar structures on the cell surface that inform cells of their neighbors and that lead to the distinction between self and non-self as a basis of our immune system and successful defense against pathogens. Understanding this molecular language of sugars is a prerequisite for the molecular understanding of many diseases such as cancer which in fact results from failed cellular communication. Recent advances in glycosciences suggest that subtle patterns of substitution, such as the pattern of sulfation in heparin, are the bearers of crucial information, e.g. for blood coagulation. And evidence is accumulating that related sugar molecules such as chitosans with a specific pattern of acetylation may interfere with this cellular communication, allowing us to influence cellular behaviour in a targeted manner. The ChitoBioEngineering project aims at establishing, through genetic, metabolic, and en-zyme engineering, biotechnological ways of producing fully defined, partially acetylated chito-san oligomers. Today’s commercially available chitosans are produced chemically from chitin isolated from shrimp shell wastes. They can be well defined concerning their degree of poly-merisation and degree of acetylation, but they are invariably characterised by a random pat-tern of acetylation (PA). We have recently hypothesised that the biological activities of chito-sans, such as their antimicrobial, plant strengthening, immuno-stimulatory or wound healing activities, should be greatly influenced by their PA. However, no methods are available today for the production of chitosans with defined non-random PA. Microbial genes will be used to drive the biosynthesis of chitosan oligomers with defined ar-chitecture, i.e. with a specific, non-random PA. We will use novel chitin synthases and chitin deacetylases stemming from our extensive gene discovery projects for heterologous expres-sion in suitable micro-organisms to drive the production of a range of such oligomers which will be fully characterised using state-of-the-art analytical tools. Advanced genetic and en-zyme engineering will optimise the expression of the genes and fine-tune the properties of the enzymes, respectively, and metabolic engineering will maximise the yield of the well de¬fined chitosans. We will use our extensive experience as well as our wide-spread network within the chitosan scientific and industrial community to analyse the biological activities of these chitosans and to explore their potential applications in different market sectors, with a focus on cosmetics and pharmaceutical applications.
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