Escherichia coli possess a large number of dedicated transporters for a wide range of carbohydrate substrates. These transporters are not constitutively expressed but rather induced in the presence of their cognate sugar. However, rarely does an organism such as E. coli see only one sugar in its natural environment as is common in traditional laboratory experiments. Rather, the organism is often confronted with multiple sugars. We hypothesize, therefore, that E. coli has evolved an additional layer of regulation that enables it to reprogram its metabolism in response to multiple sugars.

In this talk we discuss our efforts directed towards unraveling this regulation. Through the use of transcriptional reporters, we have observed a weak hierarchy in pentose utilization. For example, arabinose inhibits the expression of the xylose metabolic genes. Furthermore, deletion of the arabinose regulator, AraC, leads to increased xylose metabolic gene expression. Moreover, we also observe regulatory crosstalk by ribose and hexose sugars such as rhamnose and fucose. We have also systematically deleted all known pentose and hexose transporters both individually and in combination. Our results show significant cross-talk between the various transporters, both in terms of their specificity and also the regulation of their expression. Collectively, our results demonstrate that the regulation of individual pentose metabolism and transport pathways is interconnected to form a systems-level control system. We believe that these results will aid in the metabolic engineering of strains using pentose feedstocks, such as in biofuels production and natural product synthesis.