Alternative pathways of galactose assimilation: could inverse metabolic engineering provide an alternative to galactosemic patients?

Abstract

The galactose assimilation pathway has been extensively studied as an example of a genetic regulatory switch. Besides the importance of this pathway as a tool in basic biological research, unraveling its structure and regulation is also of major medical importance. Impairment of galactose assimilation is the cause of the genetic metabolic disease known as “galactosemia”, while the in vivo activity of the pathway affects the production of glycans. The latter have been connected to tumor metastasis, anti-cancer drug resistance and various cardiovascular diseases. Despite the vast amount of studies, however, galactose assimilation and its interaction with other parts of the metabolic network have not been fully elucidated yet. In yeast and higher eukaryotes, it is still being studied as comprising only the linear Leloir pathway. Recent observations, however, indicate that alternative pathways of galactose assimilation identified in prokaryotes and fungi might also be present in yeast. Such a result is valuable per se, because it could lead to the discovery of these pathways in humans. Even more importantly, these pathways provide alternative phenotypes with known genetic fingerprints that can be used in the context of classical and inverse metabolic engineering to examine and treat the mechanisms of defects of galactose assimilation.