The Weimberg pathway: an alternative for Myceliophthora thermophila to utilize D-xylose

With D-xylose being the second most abundant sugar in nature, its conversion into products could significantly improve biomass-based process economy. There are two well-studied phosphorylative pathways for D-xylose metabolism. One is isomerase pathway mainly found in bacteria, and the other one is oxo-reductive pathway that always exists in fungi. Except for these two pathways, there are also non-phosphorylative pathways named xylose oxidative pathways and they have several advantages over traditional phosphorylative pathways. In Myceliophthora thermophila, D-xylose can be metabolized through oxo-reductive pathway after plant biomass degradation. The survey of non-phosphorylative pathways in this filamentous fungus will offer a potential way for carbon-efficient production of fuels and chemicals using D-xylose.

In this study, an alternative for utilization of D-xylose, the non-phosphorylative Weimberg pathway was established in M. thermophila. Growth on D-xylose of strains whose D-xylose reductase gene was disrupted, was restored after overexpression of the entire Weimberg pathway. During the construction, a native D-xylose dehydrogenase with highest activity in M. thermophila was discovered. Here, M. thermophila was also engineered to produce 1,2,4-butanetriol using D-xylose through non-phosphorylative pathway. Afterwards, transcriptome analysis revealed that the D-xylose dehydrogenase gene was obviously upregulated after deletion of D-xylose reductase gene when cultured in a D-xylose medium. Besides, genes involved in growth were enriched in strains containing the Weimberg pathway.

The Weimberg pathway was established in M. thermophila to support its growth with D-xylose being the sole carbon source. Besides, M. thermophila was engineered to produce 1,2,4-butanetriol using D-xylose through non-phosphorylative pathway. To our knowledge, this is the first report of non-phosphorylative pathway recombinant in filamentous fungi, which shows great potential to convert D-xylose to valuable chemicals.