초록
<P>Rapid and effective consumption of <SMALL>D</SMALL>-xylose by <I>Saccharomyces cerevisiae</I> is essential for cost-efficient cellulosic bioethanol production. Hence, heterologous <SMALL>D</SMALL>-xylose metabolic pathways have been introduced into <I>S. cerevisiae</I>. An effective solution is based on a xylose isomerase in combination with the overexpression of the xylulose kinase (Xks1) and all genes of the non-oxidative branch of the pentose phosphate pathway. Although this strain is capable of consuming <SMALL>D</SMALL>-xylose, growth inhibition occurs at higher <SMALL>D</SMALL>-xylose concentrations, even abolishing growth completely at 8% <SMALL>D</SMALL>-xylose. The decreased growth rates are accompanied by significantly decreased ATP levels. A key ATP-utilizing step in <SMALL>D</SMALL>-xylose metabolism is the phosphorylation of <SMALL>D</SMALL>-xylulose by Xks1. Replacement of the constitutive promoter of <I>XKS1</I> by the galactose tunable promoter Pgal10 allowed the controlled expression of this gene over a broad range. By decreasing the expression levels of <I>XKS1</I>, growth at high <SMALL>D</SMALL>-xylose concentrations could be restored concomitantly with increased ATP levels and high rates of xylose metabolism. These data show that in fermentations with high <SMALL>D</SMALL>-xylose concentrations, too high levels of Xks1 cause a major drain on the cellular ATP levels thereby reducing the growth rate, ultimately causing substrate accelerated death. Hence, expression levels of <I>XKS1</I> in <I>S. cerevisiae</I> needs to be tailored for the specific growth conditions and robust <SMALL>D</SMALL>-xylose metabolism.</P><P><B>Supplementary Information</B></P><P>The online version contains supplementary material available at 10.1186/s13068-023-02320-4.</P>