Comparative Xylose Metabolism among the Ascomycetes <i>C. albicans</i>, <i>S. stipitis</i> and <i>S. cerevisiae</i>

<div><p>The ascomycetes <i>Candida albicans, Saccharomyces cerevisiae</i> and <i>Scheffersomyces stipitis</i> metabolize the pentose sugar xylose very differently. <i>S. cerevisiae</i> fails to grow on xylose, while <i>C. albicans</i> can grow, and <i>S. stipitis</i> can both grow and ferment xylose to ethanol. However, all three species contain highly similar genes that encode potential xylose reductases and xylitol dehydrogenases required to convert xylose to xylulose, and xylulose supports the growth of all three fungi. We have created <i>C. albicans</i> strains deleted for the xylose reductase gene <i>GRE3</i>, the xylitol dehydrogenase gene <i>XYL2</i>, as well as the <i>gre3 xyl2</i> double mutant. As expected, all the mutant strains cannot grow on xylose, while the single <i>gre3</i> mutant can grow on xylitol. The <i>gre3</i> and <i>xyl2</i> mutants are efficiently complemented by the <i>XYL1</i> and <i>XYL2</i> from <i>S. stipitis</i>. Intriguingly, the <i>S. cerevisiae GRE3</i> gene can complement the <i>Cagre3</i> mutant, while the <i>ScSOR1</i> gene can complement the <i>Caxyl2</i> mutant, showing that <i>S. cerevisiae</i> contains the enzymatic capacity for converting xylose to xylulose. In addition, the <i>gre3 xyl2</i> double mutant of <i>C. albicans</i> is effectively rescued by the xylose isomerase (XI) gene of either <i>Piromyces</i> or <i>Orpinomyces</i>, suggesting that the XI provides an alternative to the missing oxido-reductase functions in the mutant required for the xylose-xylulose conversion. Overall this work suggests that <i>C. albicans</i> strains engineered to lack essential steps for xylose metabolism can provide a platform for the analysis of xylose metabolism enzymes from a variety of species, and confirms that <i>S. cerevisiae</i> has the genetic potential to convert xylose to xylulose, although non-engineered strains cannot proliferate on xylose as the sole carbon source. </p> </div>