Suppressing PD-L1 Expression via AURKA Kinase Inhibition Enhances Natural Killer Cell-Mediated Cytotoxicity against Glioblastoma.

Immunotherapies have shown significant promise as an impactful strategy in cancer treatment. However, in glioblastoma multiforme (GBM), the most prevalent primary brain tumor in adults, these therapies have demonstrated lower efficacy than initially anticipated. Consequently, there is an urgent need for strategies to enhance the effectiveness of immune treatments.

OGDH and Bcl-xL loss causes synthetic lethality in glioblastoma.

Glioblastoma (GBM) remains an incurable disease, requiring more effective therapies. Through interrogation of publicly available CRISPR and RNAi library screens, we identified the α-ketoglutarate dehydrogenase (OGDH) gene, which encodes an enzyme that is part of the tricarboxylic acid (TCA) cycle, as essential for GBM growth. Moreover, by combining transcriptome and metabolite screening analyses, we discovered that loss of function of OGDH by the clinically validated drug compound CPI-613 was synthetically lethal with Bcl-xL inhibition (genetically and through the clinically validated BH3 mimetic, ABT263) in patient-derived xenografts as well neurosphere GBM cultures.

Fusobacterium nucleatum secretes amyloid-like FadA to enhance pathogenicity.

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence.

A short-chain dehydrogenase plays a key role in cellulosic D-lactic acid fermentability of Pediococcus acidilactici.

Phenolic aldehydes from lignocellulose pretreatment are strong inhibitors of cell growth and metabolism of cellulosic lactic acid bacteria. Their low solubility and recalcitrance highly reduce the removal efficiency of various detoxification methods. This study shows a simultaneous conversion of phenolic aldehydes and fermentation of D-lactic acid by Pediococcus acidilactici using corn stover feedstock.

Mechanism of Tolerance to the Lignin-Derived Inhibitor -Benzoquinone and Metabolic Modification of Biorefinery Fermentation Strains.

-Benzoquinone (BQ) is a lignin-derived inhibitor of biorefinery fermentation strains produced during pretreatment of lignocellulose. Unlike the well-studied inhibitors furan aldehydes, weak acids, and phenolics, the inhibitory properties of BQ, the microbial tolerance mechanism, and the detoxification strategy for this inhibitor have not been clearly elucidated. Here, BQ was identified as a by-product generated during acid pretreatment of various lignocellulose feedstocks, including corn stover, wheat straw, rice straw, tobacco stem, sunflower stem, and corncob residue.

Expressing an oxidative dehydrogenase gene in ethanologenic strain Zymomonas mobilis promotes the cellulosic ethanol fermentability.

Phenolic aldehydes from lignocellulose pretreatment harshly inhibit the viability and metabolism of ethanol fermenting strains. Direct conversion of phenolic aldehydes is usually incomplete due to their low water solubility and recalcitrance to bioconversion. Here we consolidated phenolic aldehydes bioconversion and ethanol fermentation in a typical ethanologenic bacterium Zymomonas mobilis by constructing an intracellular oxidative pathway.

Heterozygous diploid structure of ZN1 contributes efficient biodetoxification on solid pretreated corn stover.

Background: Fast, complete, and ultimate removal of inhibitory compounds derived from lignocellulose pretreatment is the prerequisite for efficient production of cellulosic ethanol and biochemicals. Biodetoxification is the most promising method for inhibitor removal by its unique advantages. The biodetoxification mechanisms of a unique diploid fungus responsible for highly efficient biodetoxification in solid-state culture was extensively investigated in the aspects of cellular structure, genome sequencing, transcriptome analysis, and practical biodetoxification.

Tolerance and transcriptional analysis of Corynebacterium glutamicum on biotransformation of toxic furaldehyde and benzaldehyde inhibitory compounds.

Furaldehydes and benzaldehydes are among the most toxic inhibitors from lignocellulose pretreatment on microbial growth and metabolism. The bioconversion of aldehyde inhibitors into less toxic alcohols or acids (biotransformation) is the prerequisite condition for efficient biorefinery fermentations. This study found that Corynebacterium glutamicum S9114 demonstrated excellent tolerance and biotransformation capacity to five typical aldehyde inhibitors including two furaldehydes: 2-furaldehyde (furfural), 5-(hydroxymethyl)-2-furaldehyde, and three benzaldehydes: 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin), and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde).

Converting lignin derived phenolic aldehydes into microbial lipid by Trichosporon cutaneum.

Lignin is one of the major components of lignocellulose biomass and chemically degrades into phenolic aldehydes including 4-hydroxybenzaldehyde, vanillin, and syringaldehyde. No lipid accumulation from the phenolic aldehydes by oleaginous microbes had been succeeded. Compared with vanillin and syringaldehyde, T.

Improving cellulosic ethanol fermentability of Zymomonas mobilis by overexpression of sodium ion tolerance gene ZMO0119.

Inhibition of sodium ion (Na) on Zymomonas mobilis represents an important obstacle for efficient cellulosic ethanol production. This study screened and overexpressed the genes responsible for transporting metal ions in Z. mobilis for increasing its Na tolerance.

Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by .

Background: Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain failed for accumulating glutamic acid using lignocellulose feedstock.

Results: We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by . Under excessive biotin content, induction by penicillin resulted in 41.

Tolerance response and metabolism of acetic acid by biodetoxification fungus Amorphotheca resinae ZN1.

Removal of acetic acid from pretreated lignocellulose biomass is an important step for the consequent fermentation on production of cellulosic ethanol and biobased chemicals. This study elucidates the biological metabolism and tolerance response of acetic acid by a widely used biodetoxification fungus Amorphotheca resinae ZN1. Acetic acid is consumed as a prior substrate to glucose and xylose by A.

Tolerance improvement of Corynebacterium glutamicum on lignocellulose derived inhibitors by adaptive evolution.

Robustness of fermenting strains to lignocellulose derived inhibitors is critical for efficient biofuel and biochemical productions. In this study, the industrial fermenting strain Corynebacterium glutamicum S9114 was evolved for improved inhibitor tolerance using long-term adaptive evolution by continuously transferring into the inhibitors containing corn stover hydrolysate every 24 h, and finally a stably evolved C. glutamicum was obtained after 128 days of serial transfers.

Engineering Pediococcus acidilactici with xylose assimilation pathway for high titer cellulosic l-lactic acid fermentation.

Xylose-assimilating pathways were constructed in the parental Pediococcus acidilactici strain and evolutionarily adapted to yield a highly stable co-fermentation strain for l-lactic acid production. The phosphoketolase pathway (PK) was blocked for reduction of acetic acid generation by disrupting phosphoketolase (pkt) gene. The pentose phosphate pathway (PPP) was reconstructed for xylose assimilation by integrating four heterologous genes encoding transketolase (tkt), transaldolase (tal), xylose isomerase (xylA) and xylulokinase (xylB) into the P.

Constructing xylose-assimilating pathways in Pediococcus acidilactici for high titer d-lactic acid fermentation from corn stover feedstock.

Xylose-assimilating pathway was constructed in a d-lactic acid producing Pediococcus acidilactici strain and evolutionary adapted to yield a co-fermentation strain P. acidilactici ZY15 with 97.3g/L of d-lactic acid and xylose conversion of 92.

Enhancement of furan aldehydes conversion in by elevating dehydrogenase activity and cofactor regeneration.

Background: Furfural and 5-hydroxymethylfurfural (HMF) are the two major furan aldehyde inhibitors generated from lignocellulose dilute acid pretreatment which significantly inhibit subsequent microbial cell growth and ethanol fermentation. is an important strain for cellulosic ethanol fermentation but can be severely inhibited by furfural and (or) HMF. Previous study showed that contains its native oxidoreductases to catalyze the conversion of furfural and HMF, but the corresponding genes have not been identified.

Inhibitor degradation and lipid accumulation potentials of oleaginous yeast Trichosporon cutaneum using lignocellulose feedstock.

Oleaginous yeast Trichosporon cutaneum is robust to high levels of lignocellulose derived inhibitor compounds with considerable lipid accumulation capacity. The potential of lipid accumulation of T. cutaneum ACCC 20271 was investigated using corn stover hydrolysates with varying sugar and inhibitor concentrations.

Genome sequence of Trichosporon cutaneum ACCC 20271: An oleaginous yeast with excellent lignocellulose derived inhibitor tolerance.

Oleaginous yeast Trichosporon cutaneum demonstrated excellent lipid accumulation performance and inhibitor tolerance derived from lignocellulose pretreatment. Here we firstly report a 30.45Mb assembly genome of T.

Engineering wild-type robust Pediococcus acidilactici strain for high titer L- and D-lactic acid production from corn stover feedstock.

Pediococcus acidilactici TY112 producing L-lactic acid and P. acidilactici ZP26 producing D-lactic acid, were engineered from the wild-type P. acidilactici DQ2 by ldhD or ldh gene disruption, and the robustness of the wild-type strain to the inhibitors derived from lignocellulose pretreatment was maintained well.

Transcriptome analysis of Zymomonas mobilis ZM4 reveals mechanisms of tolerance and detoxification of phenolic aldehyde inhibitors from lignocellulose pretreatment.

Background: Phenolic aldehydes generated from lignocellulose pretreatment exhibited severe toxic inhibitions on microbial growth and fermentation. Numerous tolerance studies against furfural, 5-hydroxymethyl-2-furaldehyde (HMF), acetate, and ethanol were reported, but studies on inhibition of phenolic aldehyde inhibitors are rare. For ethanologenic strains, Zymomonas mobilis ZM4 is high in ethanol productivity and genetic manipulation feasibility, but sensitive to phenolic aldehyde inhibitors.

Transcriptional analysis of Amorphotheca resinae ZN1 on biological degradation of furfural and 5-hydroxymethylfurfural derived from lignocellulose pretreatment.

Background: Furfural and 5-hydroxymethylfurfural (HMF) are the two major inhibitor compounds generated from lignocellulose pretreatment, especially for dilute acid, steam explosion, neutral hot water pretreatment methods. The two inhibitors severely inhibit the cell growth and metabolism of fermenting strains in the consequent bioconversion step. The biodetoxification strain Amorphotheca resinae ZN1 has demonstrated its extraordinary capacity of fast and complete degradation of furfural and HMF into corresponding alcohol and acid forms.

Sro7 and Sro77, the yeast homologues of the Drosophila lethal giant larvae (Lgl), regulate cell proliferation via the Rho1-Tor1 pathway.

Saccharomyces cerevisiae Sro7 and Sro77 are homologues of the Drosophila tumour suppressor lethal giant larvae (Lgl), which regulates cell polarity in Drosophila epithelial cells. Here, we showed that double mutation of SRO7/SRO77 was defective in colony growth. The colony of the SRO7/SRO77 double deletion was much smaller than the WT and appeared to be round with a smooth surface, compared with the WT.

Analysis of biodegradation performance of furfural and 5-hydroxymethylfurfural by Amorphotheca resinae ZN1.

Background: Furfural and 5-hydroxymethylfurfural (HMF) are the degradation products of lignocellulose during pretreatment operations and significantly inhibit the consequent enzymatic hydrolysis and fermentation processes. The biodetoxification fungus Amorphotheca resinae ZN1 had demonstrated its excellent capacity on degrading lignocellulose derived inhibitors and helped the fermentation processes to achieve high yield of ethanol and biochemicals. Analysis of the biological degradation performance of furfural and HMF by A.

Cloning of LicB from Clostridium thermocellum and its efficient secretive expression of thermostable β-1,3-1,4-glucanase.

β-1,3-1,4-glucanase is a widely used enzyme in brewing and in animal feed processing. To produce the bacterial enzyme at an industrial scale, the enzyme should be able to be secreted from microbial cells into fermentation broth and be stable in different conditions. In this study, the LicB gene encoding β-1,3-1,4-glucanase (lichenase) from Clostridium thermocellum was secretively expressed in a secretive strain, Bacillus subtilis WB800, with eight extracellular protease deletion which made LicB expressed obviously and reached 1.

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS).