Team:SDU-Denmark

© iGEM University of Southern Denmark 2012

Novel approach to carbohydrate intake restriction using bacterial machines as sucrose converters

The modern diet is rich in carbohydrates and though increasing awareness about the health problems related, obesity is still the sixth most important risk factor contributing to the overall burden of disease worldwide and therefore a large burden on society. For reasons unknown, risks like cardiovascular disease, type 2 diabetes and different types of cancers, that all can be related to obesity, do not seem to motivate a healthy diet in modern society. In our project we approach this problem from a new angle. Instead of changing the diet, we take a look at the mechanisms that regulate carbohydrate uptake from our daily diet. We will focus on conversion of sugars into fibers, namely inulin, that the human body is unable to digest. Apart from being indigestible inulin possesses interesting properties as a prebiotic. Inulin affect the gut microbiota by promoting ”helpful” bacteria, like bifidobacteria. Intake of short-chain inulin has been proven to lead to a significant decrease in food intake, body weight gain and fat mass development in rodents. The ultimate goal of the project will be to construct a probiotic microorganism, capable of producing inulin fibers and able to survive in the human gut for short periods of time. We will clone the genes coding for the plant enzymes Fructan:fructan 1-fructosyltransferase (1-FFT) and sucrose sucrose 1-fructosyltransferase (1-SST) that together make up the synthesis pathway of plant inulin in Helianthus tuberosus (degree of polymerization: 30-150) or a bacterial version of inulin synthase, possibly from Lactobacillus Reuteri (degree of polymerization: 20-10.000). Furthermore, we will look into other mechanisms that could regulate sugar uptake, like adding a cellulose synthase to our construct as well. Which would further increase the beneficial factor of the microorganism, by removing larger amounts of sugar from the diet, and contributing cellulose to the intestine which among other things, have a preventive effect on the development of colon cancer.

(Another positive aspect of the inulin production is that the bacteria should use a lot of the sugar we eat and convert it into the non-digestible fiber, hence lowering the energy we get from eating sucrose. Since sucrose consists of a fructose and glucose unit, there will be one glucose unit leftover for every added monomer of fructose to the inulin polymer. These glucose units could then be used as an added bonus to produce Cellulose, so that we could get additional fibers in our diet and get rid of the glucose.)