Crabtree/Warburg-like aerobic xylose fermentation by engineered Saccharomyces cerevisiae

Lee, Sae-Byuk; Tremaine, Mary; Place, Michael; Liu, Lisa; Pier, Austin; Krause, David J.; Xie, Dan; Zhang, Yaoping; Landick, Robert; Gasch, Audrey P.; Hittinger, Chris Todd; Sato, Trey K.

doi:10.1016/j.ymben.2021.09.008

Cited by 31 publications

(20 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Saccharomyces cerevisiae is the choice microbe for the industrial production of the vast majority of biofuels due to its high ethanol tolerance, high glycolytic and fermentative capacity, and amenability to genetic engineering (2). However, S. cerevisiae requires genetic engineering to metabolize xylose, and even engineered strains are often inefficient in the fermentation of lignocellulosic xylose (3)(4)(5)(6). This has led to the suggestion that cost-effective industrial conversion of xylose would be better achieved using native pentose-fermenting yeast species.…”

Section: Introductionmentioning

confidence: 99%

Codon optimization, not gene content, predicts XYLose metabolism in budding yeasts

Nalabothu

Fisher

LaBella

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Xylose is the second most abundant monomeric sugar in plant biomass. Consequently, xylose catabolism is an ecologically important trait for saprotrophic organisms, as well as a fundamentally important trait for industries that hope to convert plant mass to renewable fuels and other bioproducts using microbial metabolism. Although common across fungi, xylose catabolism is rare within Saccharomycotina, the subphylum that contains most industrially relevant fermentative yeast species. Several yeasts unable to consume xylose have been previously reported to possess complete predicted xylolytic metabolic pathways, suggesting the absence of a gene-trait correlation for xylose metabolism. Here, we measured growth on xylose and systematically identify XYL pathway orthologs across the genomes of 332 budding yeast species. We found that most yeast species possess complete predicted xylolytic pathways, but pathway presence did not correlate with xylose catabolism. We then quantified codon usage bias of XYL genes and found that codon optimization was higher in species able to consume xylose. Finally, we showed that codon optimization of XYL2, which encodes xylitol dehydrogenase, positively correlated with growth rates in xylose medium. We conclude that gene content cannot predict xylose metabolism; instead, codon optimization is now the best predictor of xylose metabolism from yeast genome sequence data.Significance StatementIn the genomic era, strategies are needed for the prediction of metabolic traits from genomic data. Xylose metabolism is an industrially important trait, but it is not found in most yeast species heavily used in industry. Because xylose metabolism appears rare across budding yeasts, we sought to identify a computational means of predicting which species are capable of xylose catabolism. We did not find a relationship between gene content and xylose metabolism traits. Rather, we found that codon optimization of xylolytic genes was higher in species that can metabolize xylose, and that optimization of one specific gene correlated with xylose-specific growth rates. Thus, codon optimization is currently the only means of accurately predicting xylose metabolism from genome sequence data.

show abstract

Section: Introductionmentioning

confidence: 99%

Codon optimization, not gene content, predicts XYLose metabolism in budding yeasts

Nalabothu

Fisher

LaBella

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lignocellulosic biomass, such as energy crops, aquatic plants, forest biomass, and agricultural residues, is one of the most important renewable sources. Biofuels from lignocellulosic biomass has been considered as a good alternative to petroleum fuels due to the reduction of CO 2 emission [ 1 , 2 ]. The second generation bioethanol had been developed using lignocellulosic biomass to supply liquid fuel for vehicles [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Protein acetylation regulates xylose metabolism during adaptation of Saccharomyces cerevisiae

Tan

Wang

et al. 2021

Biotechnol Biofuels

View full text Add to dashboard Cite

Background As the second most abundant polysaccharide in nature, hemicellulose can be degraded to xylose as the feedstock for bioconversion to fuels and chemicals. To enhance xylose conversion, the engineered Saccharomyces cerevisiae with xylose metabolic pathway is usually adapted with xylose as the carbon source in the laboratory. However, the mechanism under the adaptation phenomena of the engineered strain is still unclear. Results In this study, xylose-utilizing S. cerevisiae was constructed and used for the adaptation study. It was found that xylose consumption rate increased 1.24-fold in the second incubation of the yYST12 strain in synthetic complete-xylose medium compared with the first incubation. The study figured out that it was observed at the single-cell level that the stagnation time for xylose utilization was reduced after adaptation with xylose medium in the microfluidic device. Such transient memory of xylose metabolism after adaptation with xylose medium, named “xylose consumption memory”, was observed in the strains with both xylose isomerase pathway and xylose reductase and xylitol dehydrogenase pathways. In further, the proteomic acetylation of the strains before and after adaptation was investigated, and it was revealed that H4K5 was one of the most differential acetylation sites related to xylose consumption memory of engineered S. cerevisiae. We tested 8 genes encoding acetylase or deacetylase, and it was found that the knockout of the GCN5 and HPA2 encoding acetylases enhanced the xylose consumption memory. Conclusions The behavior of xylose consumption memory in engineered S. cerevisiae can be successfully induced with xylose in the adaptation. H4K5Ac and two genes of GCN5 and HPA2 are related to xylose consumption memory of engineered S. cerevisiae during adaptation. This study provides valuable insights into the xylose adaptation of engineered S. cerevisiae.

show abstract

“…Even S. cerevisiae engineered for xylose metabolism does not recognize xylose as a fermentable carbon source but exhibits a respiratory response ( Jin et al, 2004 ). Respiration was required for yeast cells to achieve sufficient energy to growth on xylose aerobically ( Lee S. B. et al, 2021 ). As reported previously, shifted metabolic state from fermentation to respiration could be achieved by deletion of SPT10 , SWI6 , and ASF1 , which function in altering chromatin structure ( Galdieri et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Deletion of NGG1 in a recombinant Saccharomyces cerevisiae improved xylose utilization and affected transcription of genes related to amino acid metabolism

et al. 2022

View full text Add to dashboard Cite

Production of biofuels and biochemicals from xylose using yeast cell factory is of great interest for lignocellulosic biorefinery. Our previous studies revealed that a natural yeast isolate Saccharomyces cerevisiae YB-2625 has superior xylose-fermenting ability. Through integrative omics analysis, NGG1, which encodes a transcription regulator as well as a subunit of chromatin modifying histone acetyltransferase complexes was revealed to regulate xylose metabolism. Deletion of NGG1 in S. cerevisiae YRH396h, which is the haploid version of the recombinant yeast using S. cerevisiae YB-2625 as the host strain, improved xylose consumption by 28.6%. Comparative transcriptome analysis revealed that NGG1 deletion down-regulated genes related to mitochondrial function, TCA cycle, ATP biosynthesis, respiration, as well as NADH generation. In addition, the NGG1 deletion mutant also showed transcriptional changes in amino acid biosynthesis genes. Further analysis of intracellular amino acid content confirmed the effect of NGG1 on amino acid accumulation during xylose utilization. Our results indicated that NGG1 is one of the core nodes for coordinated regulation of carbon and nitrogen metabolism in the recombinant S. cerevisiae. This work reveals novel function of Ngg1p in yeast metabolism and provides basis for developing robust yeast strains to produce ethanol and biochemicals using lignocellulosic biomass.

show abstract

Crabtree/Warburg-like aerobic xylose fermentation by engineered Saccharomyces cerevisiae

Cited by 31 publications

References 66 publications

Codon optimization, not gene content, predicts XYLose metabolism in budding yeasts

Codon optimization, not gene content, predicts XYLose metabolism in budding yeasts

Protein acetylation regulates xylose metabolism during adaptation of Saccharomyces cerevisiae

Deletion of NGG1 in a recombinant Saccharomyces cerevisiae improved xylose utilization and affected transcription of genes related to amino acid metabolism

Contact Info

Product

Resources

About