Search PubMedSearch

SEARCH · Search PubMed

Results for “Xylose”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

7 recordsLinked to original sources

Engineering of xylose metabolic pathways in Rhodotorula toruloides for sustainable biomanufacturing.

The oleaginous yeast Rhodotorula toruloides is a promising microbial cell factory for the sustainable production of biofuels and value-added chemicals from renewable carbon sources. Unlike the conventional yeast Saccharomyces cerevisiae, R. toruloides can naturally metabolize xylose, the second most abundant sugar in lignocellulosic hydrolysates. However, its native xylose metabolism is inefficient, characterized by slow xylose uptake and accumulation of D-arabitol. Moreover, despite its phenotype, research on the enzymes involved in xylose metabolism has yet to reach a consensus. Therefore, this review provides a comprehensive analysis of the non-canonical xylose metabolism in R. toruloides, focusing on the properties of key enzymes involved in xylose metabolism. Native xylose reductase and xylitol dehydrogenase exhibit broad substrate promiscuity compared to their counterparts in the xylose-fermenting Scheffersomyces stipitis. Additionally, the absence of xylulokinase expression under xylose-utilizing conditions redirects metabolism toward D-arabitol accumulation. Consequently, D-arabitol dehydrogenases and ribulokinase play essential roles in the xylose metabolism of R. toruloides. These findings highlight the fundamental differences between R. toruloides xylose metabolism and the oxidoreductase pathways observed in other xylose-fermenting yeast, providing insights for metabolic engineering strategies to improve xylose utilization and enhance bioconversion of cellulosic hydrolysates to different bioproducts by R. toruloides.

Xylose

Structural genome variation drives adaptation of the xylose-fermenting yeast Scheffersomyces stipitis to lignocellulosic hydrolysates.

Second-generation (2G) bioethanol from lignocellulosic feedstocks is a sustainable alternative to fossil fuels. However, its production is constrained by the poor performance of industrial microbes in hydrolysates that are generated during biomass pretreatment. Scheffersomyces stipitis is a native xylose fermenting yeast and a promising platform for 2G bioethanol production, and adaptive evolution under hydrolysate stress has yielded strains with enhanced performance. However, the chromosomal basis of this adaptation is unknown. Here, we demonstrate that chromosome scale structural variation, rather than point mutations, underlies the improved phenotype of the evolved strains. By integrating long- and short-read genome sequencing, we identify two major chromosomal rearrangements in the top performing isolate: a reciprocal translocation between chromosomes 1 and 2 that disrupts the NUDIX hydrolase gene YSA1, and the formation of a mitotically stable 175 kb minichromosome derived from chromosome 5. Functional analyses show that disruption of YSA1 enhances xylose utilisation and ethanol yield, while the minichromosome contributes to improved performance in hydrolysate conditions. These findings provide direct evidence that balanced rearrangements and minichromosome formation can be selected during prolonged stress and can generate adaptive phenotypes. Taken together, our study establishes genome reorganisation as a key driver of adaptation in S. stipitis.

Xylose

Versatile sugar and valerate metabolic pathways in Paraburkholderia xenovorans LB400 enable tailored poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production.

Poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) polymers are accumulated by diverse prokaryotes. Their distinct monomer compositions enable their use as tailored bioplastics. The aims were to characterize the poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis by Paraburkholderia xenovorans LB400 using different sugars and valerate, and to gain genome-oriented insights into polyhydroxyalkanoate production. d-Glucose, d-mannitol, d-gluconate, and d-xylose were evaluated as sole carbon sources or supplemented with valerate. Polyhydroxyalkanoates synthesized by strain LB400 were characterized through GC-MS, GC-FID, FTIR, and 1H and 13C-NMR. P. xenovorans LB400 reached 1.00-1.39 g L-1 of dry cell weight (DCW) with a P(3HB) content of 21-43% w w-1 when grown on different sugars. The addition of valerate to the sugar-grown LB400 cultures yielded a DCW of 1.79 to 2.29 g L-1 and a P(3HB-co-3HV) content of 50.0‒51.2% w w-1, with varying 3HV compositions (28‒43 mol%). The highest 3HV incorporation was observed with d-xylose and valerate. Genomic analyses of strain LB400 revealed key elements of sugar metabolism influencing growth, polymer accumulation, and monomer composition. LB400 genome encodes the PhaJ-like R-specific hydratase and FadJ epimerase, which are potentially useful for modulating copolymer composition. PHA production under bioreactor conditions was evaluated. In a bioreactor fed with d-glucose, LB400 achieved a P(3HB) concentration of 2.2 g L-1. These findings highlight the metabolic versatility of P. xenovorans LB400 in utilizing diverse sugars to produce either P(3HB) or tailor-made P(3HB-co-3HV), supporting the development of bioplastics for specific applications. KEY POINTS: • Strain LB400 produced P(3HB-co-3HV) from various sugars and valerate. • Sugar type drives LB400 PHA copolymer synthesis and composition. • Strain LB400 PHA production was scaled up to a bioreactor.

Polyesters

Barcoded mutant library enables high-throughput functional genomics in a filamentous fungus.

Advances in sequencing technology enabling rapid and inexpensive whole-genome sequencing highlight how few genes are functionally characterized. This problem is particularly acute in filamentous fungi, where even in the best studied organisms upward of half of genes are poorly characterized or unannotated. High-throughput tools to identify gene function exist for single-celled organisms, like yeast and bacteria. However, filamentous fungi present challenges to high-throughput gene characterization, including low transformation efficiency and multinucleate cells. Filamentous fungi are critical components of nutrient cycling in ecosystems, form symbioses with plants that improve nutrient uptake, and are devastating human, plant, and animal pathogens causing millions of deaths and substantial crop loss each year. Thus, it is critical to overcome challenges to rapid gene characterization in filamentous fungi. We generated a library of hundreds of millions of uniquely barcoded plasmids containing a broad host-range drug resistance marker for ectopic insertion into filamentous fungal genomes by Agrobacterium tumefaciens. We then optimized A. tumefaciens mediated transformation of the biocontrol agent Trichoderma atroviride and made an insertional mutagenesis library containing 83,311 barcoded insertions, disrupting 5,331 of 11,863 predicted genes. This library enables high-throughput screens to rapidly connect genotype to phenotype. Quantifying relative barcode abundance in the pooled library before and after exposure to experimental conditions identified candidate genes and recovered known pathway components in amino acid biosynthetic, fructose utilization, and xylose utilization pathways. This resource establishes a scalable platform for high-throughput functional genomics in filamentous fungi, enabling investigations of fungal biology to improve medical outcomes, biotechnology, and sustainable agriculture.

Genomics

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Graft vs Host Disease

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

Bacteroides ovatus