Improved Xylitol Production from d‑Arabitol by Enhancing the Coenzyme Regeneration Efficiency of the Pentose Phosphate Pathway in Gluconobacter oxydans

Gluconobacter oxydans is used to produce xylitol from d-arabitol. This study aims to improve xylitol production by increasing the coenzyme regeneration efficiency of the pentose phosphate pathway in <i>G. oxydans</i>. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were overexpressed in <i>G. oxydans</i>. Real-time PCR and enzyme activity assays revealed that G6PDH/6PGDH activity and coenzyme regeneration efficiency increased in the recombinant <i>G. oxydans</i> strains. Approximately 29.3 g/L xylitol was obtained, with a yield of 73.2%, from 40 g/L d-arabitol in the batch biotransformation with the <i>G. oxydans</i> PZ strain. Moreover, the xylitol productivity (0.62 g/L/h) was 3.26-fold of the wild type strain (0.19 g/L/h). In repetitive batch biotransformation, the <i>G. oxydans</i> PZ cells were used for five cycles without incurring a significant loss in productivity. These results indicate that the recombinant <i>G. oxydans</i> PZ strain is economically feasible for xylitol production in industrial bioconversion

Association results for SNPs between Clear and CHB patients.

<p>SNP: single nucleotide polymorphisms, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients. P values, ORs and 95% CIs were calculated by multiple logistic regression adjusting for gender and age; - means differences could not be detected.</p><p>^a means additive model: the first genotype/the second genotype</p><p>^bmeans additive model: the first genotype/the third genotype</p><p>^cmeans recessive model: the first genotype/the second +the third genotype</p><p>^dmeans allele model.</p><p>Association results for SNPs between Clear and CHB patients.</p

Stratification analysis for age ≥ 35 years between Clear and CHB.

<p>SNP: single nucleotide polymorphisms, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients. P values, ORs and 95% CIs were calculated by multiple logistic regression adjusting for gender; - means differences could not be detected.</p><p>^a means additive model: the first genotype/the second genotype</p><p>^bmeans additive model: the first genotype/the third genotype</p><p>^cmeans recessive model: the first genotype/the second +the third genotype</p><p>^dmeans allele model.</p><p>Stratification analysis for age ≥ 35 years between Clear and CHB.</p

Linkage disequilibrium analysis of the SNPs rs12206945, rs10485138, and rs6909880 located in ASCC3 gene in HBV clearance population (n = 382) generated by HaploView 4.2 software.

<p>Linkage disequilibrium analysis of the SNPs rs12206945, rs10485138, and rs6909880 located in ASCC3 gene in HBV clearance population (n = 382) generated by HaploView 4.2 software.</p

Correlations between ASCC3 Gene Polymorphisms and Chronic Hepatitis B in a Chinese Han Population

<div><p>We have previously identified 8 SNPs in Han Chinese HBV carriers that are associated with disease progression. Although not well studied, genetic factors may also play a significant role in developing chronic HBV disease after exposure. We extend the effect of these eight SNPs on persistent HBV infection in this study. A total of 875 unrelated Han Chinese, 493 chronic hepatitis B subjects (CHB) and 382 HBV clearance individuals (Clear), were recruited from Hubei Province from September 2007 to March 2010. SNPs were verified by using TaqMan 7900HT Sequence Detection System. By using multiple logistic regression analysis, each of the 8 SNP associations was tested using 3 different genetic models (Dominant, Recessive and Additive model), in 4 types of analyses (full sample, men, women, age stratified). A Bonferroni correction was used to account for multiple statistical tests for each SNP association (P<0.05/8 = 0.0063). A significant correlation was observed at SNP rs10485138 located in ASCC3 gene in female patients (OR, 0.445; 95% CI, 0.253–0.784; <i>P</i> = 0.005). Females bearing C allele infected by HBV had an increased susceptibility to CHB compared with those T allele carriers. Our results indicated that SNP rs10485138 located in ASCC3 gene was associated with persistent HBV infection in Han Chinese.</p></div

Stratification analysis for sex between Clear and CHB in male patients.

<p>SNP: single nucleotide polymorphisms, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients. P values, ORs and 95% CIs were calculated by multiple logistic regression adjusting for age; - means differences could not be detected.</p><p>^a means additive model: the first genotype/the second genotype</p><p>^bmeans additive model: the first genotype/the third genotype</p><p>^cmeans recessive model: the first genotype/the second +the third genotype</p><p>^dmeans allele model.</p><p>Stratification analysis for sex between Clear and CHB in male patients.</p

Characteristics of variants.

<p>SNP: single nucleotide polymorphisms, Chr: chromosome, Location: Genomic position (NCBI Build 36), Allele: minor allele/major allele, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients.</p><p>Characteristics of variants.</p

Association of SNP rs10485138 with HBeAg status inCHB group.

<p>^aadditive model TT/TC</p><p>^badditive model TT/CC</p><p>^crecessive model TT/TT+TC</p><p>^ddominant model TT+TC/CC. Multiple logistic regression under three genetic models with adjustment for gender and age was used to test P value, OR and 95%CI.</p><p>Association of SNP rs10485138 with HBeAg status inCHB group.</p

Stratification analysis for sex between Clear and CHB in female patients.

<p>SNP: single nucleotide polymorphisms, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients. P values, ORs and 95% CIs were calculated by multiple logistic regression adjusting for age; - means differences could not be detected.</p><p>^a means additive model: the first genotype/the second genotype</p><p>^bmeans additive model: the first genotype/the third genotype</p><p>^cmeans recessive model: the first genotype/the second +the third genotype</p><p>^dmeans allele model.</p><p>Stratification analysis for sex between Clear and CHB in female patients.</p

Clinical and demographic characteristics of participants.

<p>M: male, F: female, Y: years, SD: standard deviation, no.: number, Clear: spontaneously recovered individuals with history of HBV infection, CHB: chronic hepatitis B patients. ALT: alanine transaminase, AST: aspartate aminotransferase, No means non-detected. The differences of clinical characteristics were calculated using chi-square test and independent sample t-test.</p><p>Clinical and demographic characteristics of participants.</p