Comparative global metabolite profiling of xylose-fermenting Saccharomyces cerevisiae SR8 and Scheffersomyces stipitis.

Bioconversion of lignocellulosic biomass into ethanol requires efficient xylose fermentation. Previously, we developed an engineered Saccharomyces cerevisiae strain, named SR8, through rational and inverse metabolic engineering strategies, thereby improving its xylose fermentation and ethanol production. However, its fermentation characteristics have not yet been fully evaluated. In this study, we investigated the xylose fermentation and metabolic profiles for ethanol production in the SR8 strain compared with native Scheffersomyces stipitis. The SR8 strain showed a higher maximum ethanol titer and xylose consumption rate when cultured with a high concentration of xylose, mixed sugars, and under anaerobic conditions than Sch. stipitis. However, its ethanol productivity was less on 40 g/L xylose as the sole carbon source, mainly due to the formation of xylitol and glycerol. Global metabolite profiling indicated different intracellular production rates of xylulose and glycerol-3-phosphate in the two strains. In addition, compared with Sch. stipitis, SR8 had increased abundances of metabolites from sugar metabolism and decreased abundances of metabolites from energy metabolism and free fatty acids. These results provide insights into how to control and balance redox cofactors for the production of fuels and chemicals from xylose by the engineered S. cerevisiae.

Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. METHODS: Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. RESULTS: Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. CONCLUSIONS: We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.

Physiological and Metabolomic Analysis of Issatchenkia orientalis MTY1 With Multiple Tolerance for Cellulosic Bioethanol Production.

Yeast with multiple tolerance onto harsh conditions has a number of advantages for bioethanol production. In this study, an alcohol yeast of Issatchenkia orientalis MTY1 is isolated in a Korean winery and its multiple tolerance against high temperature and acidic conditions is characterized in microaerobic batch cultures and by metabolomic analysis. In a series of batch cultures using 100 g L-1 glucose, I. orientalis MTY1 possesses wider growth ranges at pH 2-8 and 30-45 °C than a conventional yeast of Saccharomyces cerevisiae D452-2. Moreover, I. orientalis MTY1 showes higher cell growth and ethanol productivity in the presence of acetic acid or furfural than S. cerevisiae D452-2. I. orientalis MTY1 produces 41.4 g L-1 ethanol with 1.5 g L-1 h-1 productivity at 42 °C and pH 4.2 in the presence of 4 g L-1 acetic acid, whereas a thermo-tolerant yeast of Kluyvermyces marxianus ATCC36907 does not grow. By metabolomics by GC-TOF MS and statistical analysis of 125 metabolite peaks, it is revealed that the thermo-tolerance of I. orientalis MTY1 might be ascribed to higher contents of unsaturated fatty acids, purines and pyrimidines than S. cerevisiae D452-2. Conclusively, I. orientalis MTY1 could be a potent workhorse with multiple tolerance against harsh conditions considered in cellulosic bioethanol production.