Recent progress in the microbial production of xylonic acid.

Interest in the production of renewable chemicals from biomass has increased in the past years. Among these chemicals, carboxylic acids represent a significant part of the most desirable bio-based products. Xylonic acid is a five-carbon sugar-acid obtained from xylose oxidation that can be used in several industrial applications, including food, pharmaceutical, and construction industries. So far, the production of xylonic acid has not yet been available at an industrial scale; however, several microbial bio-based production processes are under development. This review summarizes the recent advances in pathway characterization, genetic engineering, and fermentative strategies to improve xylonic acid production by microorganisms from xylose or lignocellulosic hydrolysates. In addition, the strengths of the available microbial strains and processes and the major requirements for achieving biotechnological production of xylonic acid at a commercial scale are discussed. Efficient native and engineered microbial strains have been reported. Xylonic acid titers as high as 586 and 171 g L-1 were obtained from bacterial and yeast strains, respectively, in a laboratory medium. Furthermore, relevant academic and industrial players associated with xylonic acid production will be presented.

Engineering Zymomonas mobilis for the Production of Xylonic Acid from Sugarcane Bagasse Hydrolysate.

Sugarcane bagasse is an agricultural residue rich in xylose, which may be used as a feedstock for the production of high-value-added chemicals, such as xylonic acid, an organic acid listed as one of the top 30 value-added chemicals on a NREL report. Here, Zymomonas mobilis was engineered for the first time to produce xylonic acid from sugarcane bagasse hydrolysate. Seven coding genes for xylose dehydrogenase (XDH) were tested. The expression of XDH gene from Paraburkholderia xenovorans allowed the highest production of xylonic acid (26.17 ± 0.58 g L-1) from 50 g L-1 xylose in shake flasks, with a productivity of 1.85 ± 0.06 g L-1 h-1 and a yield of 1.04 ± 0.04 gAX/gX. Deletion of the xylose reductase gene further increased the production of xylonic acid to 56.44 ± 1.93 g L-1 from 54.27 ± 0.26 g L-1 xylose in a bioreactor. Strain performance was also evaluated in sugarcane bagasse hydrolysate as a cheap feedstock, which resulted in the production of 11.13 g L-1 xylonic acid from 10 g L-1 xylose. The results show that Z. mobilis may be regarded as a potential platform for the production of organic acids from cheap lignocellulosic biomass in the context of biorefineries.

Xylitol Production: Identification and Comparison of New Producing Yeasts.

Xylitol is a sugar alcohol with five carbons that can be used in the pharmaceutical and food industries. It is industrially produced by chemical route; however, a more economical and environmentally friendly production process is of interest. In this context, this study aimed to select wild yeasts able to produce xylitol and compare their performance in sugarcane bagasse hydrolysate. For this, 960 yeast strains, isolated from soil, wood, and insects have been prospected and selected for the ability to grow on defined medium containing xylose as the sole carbon source. A total of 42 yeasts was selected and their profile of sugar consumption and metabolite production were analyzed in microscale fermentation. The six best xylose-consuming strains were molecularly identified as Meyerozyma spp. The fermentative kinetics comparisons on defined medium and on sugarcane bagasse hydrolysate showed physiological differences among these strains. Production yields vary from YP/S = 0.25 g/g to YP/S = 0.34 g/g in defined medium and from YP/S = 0.41 g/g to YP/S = 0.60 g/g in the hydrolysate. Then, the xylitol production performance of the best xylose-consuming strain obtained in the screening, which was named M. guilliermondii B12, was compared with the previously reported xylitol producing yeasts M. guilliermondii A3, Spathaspora sp. JA1, and Wickerhamomyces anomalus 740 in sugarcane bagasse hydrolysate under oxygen-limited conditions. All the yeasts were able to metabolize xylose, but W. anomalus 740 showed the highest xylitol production yield, reaching a maximum of 0.83 g xylitol/g of xylose in hydrolysate. The screening strategy allowed identification of a new M. guilliermondii strain that efficiently grows in xylose even in hydrolysate with a high content of acetic acid (~6 g/L). In addition, this study reports, for the first time, a high-efficient xylitol producing strain of W. anomalus, which achieved, to the best of our knowledge, one of the highest xylitol production yields in hydrolysate reported in the literature.

Drug-Related Problems Identified in a Sample of Portuguese Institutionalised Elderly Patients and Pharmacists' Interventions to Improve Safety and Effectiveness of Medicines.

BACKGROUND: Currently, people live longer but often with poor quality of life. The decrease in healthy life-years is partly attributable to the institution of polypharmacy to treat various comorbidities. OBJECTIVES: The objectives of the study were to determine the prevalence and nature of drug-related problems (DRPs) in polypharmacy elderly patients residing in nursing homes and to test the acceptability of a pharmacist's intervention. METHODS: An exposure cohort was constituted in three Portuguese nursing homes, where all polypharmacy (five or more medicines) elderly patients (≥65 years of age) were analysed and then a random stratified sample was extracted to be subject to an intervention. Clinical and therapeutic data were collected and analysed for DRPs and classified according to the II Granada Consensus, by a pharmacist-led team. The intervention was the formulation of a pharmacist's recommendations to prescribers addressing clinically relevant DRPs, along with suggestions for therapy changes. RESULTS: The initial sample included 126 elderly patients taking 1332 medicines, where 2109 DRPs were identified. The exposure cohort included 63 patients, with comparable baseline data (p > 0.005). Manifest DRPs occurred in 31.7 % of the intervention group (mainly quantitative ineffectiveness-DRP 4), whereas potential DRPs were identified in 100 % of patients (mainly non-quantitative unsafe-DRP 5). Amongst the DRPs identified, 584 (56.7 %) were reported to prescribers (all types of DRPs) and 113 (11 %) to nurses (only non-quantitative ineffectiveness-DRP 3). A total of 539 pharmacist recommendations were presented to physicians, corresponding to 62 letters sent by mail, each including an average of 8.7 recommendations to solve DRPs present in intervention group (IG) patients. There was a high non-response rate (n = 34 letters; 54.8 %; containing 367 pharmacist recommendations; 68.1 %) and amongst recommendations receiving feedback, only 8.7 % of pharmacist recommendations made were accepted (n = 15). Positive responses were significantly associated with a lower number of recommendations made, whereas a higher number of recommendations increased the odds of no response (p < 0.001). CONCLUSION: A pharmacist-led medication review proved useful in identifying DRPs in elderly polypharmacy nursing home residents. Stronger bonds must be developed between healthcare professionals to increase patient safety in the vulnerable institutionalised elderly population.