Model-based contextualization of in vitro toxicity data quantitatively predicts in vivo drug response in patients.

Understanding central mechanisms underlying drug-induced toxicity plays a crucial role in drug development and drug safety. However, a translation of cellular in vitro findings to an actual in vivo context remains challenging. Here, physiologically based pharmacokinetic (PBPK) modeling was used for in vivo contextualization of in vitro toxicity data (PICD) to quantitatively predict in vivo drug response over time by integrating multiple levels of biological organization.

The trade-off of availability and growth inhibition through copper for the production of copper-dependent enzymes by Pichia pastoris.

Background: Copper is an essential chemical element for life as it is a part of prosthetic groups of enzymes including super oxide dismutase and cytochrome c oxidase; however, it is also toxic at high concentrations. Here, we present the trade-off of copper availability and growth inhibition of a common host used for copper-dependent protein production, Pichia pastoris.

Results: At copper concentrations ranging from 0.

Characterization of rhamnolipids by liquid chromatography/mass spectrometry after solid-phase extraction.

Rhamnolipids are surface-active agents with a broad application potential that are produced in complex mixtures by bacteria of the genus Pseudomonas. Analysis from fermentation broth is often characterized by laborious sample preparation and requires hyphenated analytical techniques like liquid chromatography coupled to mass spectrometry (LC-MS) to obtain detailed information about sample composition. In this study, an analytical procedure based on chromatographic method development and characterization of rhamnolipid sample material by LC-MS as well as a comparison of two sample preparation methods, i.

Ustilago maydis produces itaconic acid via the unusual intermediate trans-aconitate.

Itaconic acid is an important biomass-derived chemical building block but has also recently been identified as a metabolite produced in mammals, which has antimicrobial activity. The biosynthetic pathway of itaconic acid has been elucidated in the ascomycetous fungus Aspergillus terreus and in human macrophages. In both organisms itaconic acid is generated by decarboxylation of the tricarboxylic acid (TCA) cycle intermediate cis-aconitate.

A minimal growth medium for the basidiomycete for metabolic flux analysis.

Background: secretes a huge enzymatic repertoire including hydrolytic and oxidative enzymes and is an example for higher basidiomycetes being interesting for biotechnology. The complex growth media used for submerged cultivation limit basic physiological analyses of this group of organisms. Using undefined growth media, only little insights into the operation of central carbon metabolism and biomass formation, , the interplay of catabolic and anabolic pathways, can be gained.

Prospecting the biodiversity of the fungal family Ustilaginaceae for the production of value-added chemicals.

Background: Ustilaginaceae (belonging to the smut fungi) are commonly known for their plant pathogenicity. Although these microbes lead to yield reduction of cereal production, they can also have an economically positive side. Ustilaginaceae naturally produce a versatile range of value-added chemicals with potential applications in the food, pharmaceutical, and chemical industry.

Multi-capillary column-ion mobility spectrometry of volatile metabolites emitted by Saccharomyces cerevisiae.

Volatile organic compounds (VOCs) produced during microbial fermentations determine the flavor of fermented food and are of interest for the production of fragrances or food additives. However, the microbial synthesis of these compounds from simple carbon sources has not been well investigated so far. Here, we analyzed the headspace over glucose minimal salt medium cultures of Saccharomyces cerevisiae using multi-capillary column-ion mobility spectrometry (MCC-IMS).

Metabolite transfer with the fermentation product 2,3-butanediol enhances virulence by Pseudomonas aeruginosa.

The respiratory tract of cystic fibrosis (CF) patients harbor persistent microbial communities (CF airway microbiome) with Pseudomonas aeruginosa emerging as a dominant pathogen. Within a polymicrobial infection, interactions between co-habitant microbes can be important for pathogenesis, but even when considered, these interactions are not well understood. Here, we show with in vitro experiments that, compared with glucose, common fermentation products from co-habitant bacteria significantly increase virulence factor production, antimicrobial activity and biofilm formation of P.

Identification of an endo-1,4-beta-xylanase of Ustilago maydis.

Background: The utilization of raw biomass components such as cellulose or hemicellulose for the production of valuable chemicals has attracted considerable research interest in recent years. One promising approach is the application of microorganisms that naturally convert biomass constituents into value added chemicals. One of these organisms--Ustilago maydis--can grow on xylan, the second most abundant polysaccharide in nature, while at the same time it produces chemicals of biotechnological interest.

From measurement to implementation of metabolic fluxes.

The intracellular reaction rates (fluxes) are the ultimate outcome of the activities of the complete inventory (from DNA to metabolite) and in their sum determine the cellular phenotype. The genotype-phenotype relationship is fundamental in such different fields as cancer research and biotechnology. Here, we summarize the developments in determining metabolic fluxes, inferring major pathways from the DNA-sequence, estimating optimal flux distributions, and how these flux distributions can be achieved in vivo.