doubles the number of metabolite and exposome annotations in human plasma using an Orbitrap Astral mass spectrometer.

Chemical exposures may impact human metabolism and contribute to the etiology of neurodegenerative disorders like Alzheimer's Disease (AD). Identifying these small metabolites involves matching experimental spectra to reference spectra in databases. However, environmental chemicals or physiologically active metabolites are usually present at low concentrations in human specimens.

High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling.

Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria.

Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S.

Simultaneous Quantitation and Discovery (SQUAD) Analysis: Combining the Best of Targeted and Untargeted Mass Spectrometry-Based Metabolomics.

Untargeted and targeted approaches are the traditional metabolomics workflows acquired for a wider understanding of the metabolome under focus. Both approaches have their strengths and weaknesses. The untargeted, for example, is maximizing the detection and accurate identification of thousands of metabolites, while the targeted is maximizing the linear dynamic range and quantification sensitivity.

Lignin deconstruction by anaerobic fungi.

Lignocellulose forms plant cell walls, and its three constituent polymers, cellulose, hemicellulose and lignin, represent the largest renewable organic carbon pool in the terrestrial biosphere. Insights into biological lignocellulose deconstruction inform understandings of global carbon sequestration dynamics and provide inspiration for biotechnologies seeking to address the current climate crisis by producing renewable chemicals from plant biomass. Organisms in diverse environments disassemble lignocellulose, and carbohydrate degradation processes are well defined, but biological lignin deconstruction is described only in aerobic systems.

Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts.

Background: Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption.

Engineering site-selective incorporation of fluorine into polyketides.

Although natural products and synthetic small molecules both serve important medicinal functions, their structures and chemical properties are relatively distinct. To expand the molecular diversity available for drug discovery, one strategy is to blend the effective attributes of synthetic and natural molecules. A key feature found in synthetic compounds that is rare in nature is the use of fluorine to tune drug behavior.

Downregulation of Squalene Synthase Broadly Impacts Isoprenoid Biosynthesis in Guayule.

Production of natural rubber by (guayule) requires increased yield for economic sustainability. An RNAi gene silencing strategy was used to engineer isoprenoid biosynthesis by downregulation of squalene synthase (SQS), such that the pool of farnesyl diphosphate (FPP) substrate might instead be available to initiate natural rubber synthesis. Downregulation of SQS resulted in significantly reduced squalene and slightly increased rubber, but not in the same tissues nor to the same extent, partially due to an apparent negative feedback regulatory mechanism that downregulated mevalonate pathway isoprenoid production, presumably associated with excess geranyl pyrophosphate levels.

Adaptive evolution of Methylotuvimicrobium alcaliphilum to grow in the presence of rhamnolipids improves fatty acid and rhamnolipid production from CH4.

Rhamnolipids (RLs) are well-studied biosurfactants naturally produced by pathogenic strains of Pseudomonas aeruginosa. Current methods to produce RLs in native and heterologous hosts have focused on carbohydrates as production substrate; however, methane (CH4) provides an intriguing alternative as a substrate for RL production because it is low cost and may mitigate greenhouse gas emissions. Here, we demonstrate RL production from CH4 by Methylotuvimicrobium alcaliphilum DSM19304.

In-planta production of the biodegradable polyester precursor 2-pyrone-4,6-dicarboxylic acid (PDC): Stacking reduced biomass recalcitrance with value-added co-product.

2-Pyrone-4,6-dicarboxylic acid (PDC), a chemically stable intermediate that naturally occurs during microbial degradation of lignin by bacteria, represents a promising building block for diverse biomaterials and polyesters such as biodegradable plastics. The lack of a chemical synthesis method has hindered large-scale utilization of PDC and metabolic engineering approaches for its biosynthesis have recently emerged. In this study, we demonstrate a strategy for the production of PDC via manipulation of the shikimate pathway using plants as green factories.

Omics-Driven Biotechnology for Industrial Applications.

Biomanufacturing is a key component of biotechnology that uses biological systems to produce bioproducts of commercial relevance, which are of great interest to the energy, material, pharmaceutical, food, and agriculture industries. Biotechnology-based approaches, such as synthetic biology and metabolic engineering are heavily reliant on "omics" driven systems biology to characterize and understand metabolic networks. Knowledge gained from systems biology experiments aid the development of synthetic biology tools and the advancement of metabolic engineering studies toward establishing robust industrial biomanufacturing platforms.

Engineering Saccharomyces cerevisiae for isoprenol production.

Isoprenol (3-methyl-3-butene-1-ol) is a valuable drop-in biofuel and an important precursor of several commodity chemicals. Synthetic microbial systems using the heterologous mevalonate pathway have recently been developed for the production of isoprenol in Escherichia coli, and a significant yield and titer improvement has been achieved through a decade of research. Saccharomyces cerevisiae has been widely used in the biotechnology industry for isoprenoid production, but there has been no good example of isoprenol production reported in this host.

Pre-meal and postprandial lipaemia in subjects with the metabolic syndrome: effects of timing and protein quality (randomised crossover trial).

Non-fasting TAG - postprandial lipaemia (PPL) - are to a higher degree associated with cardiovascular risk compared with fasting TAG. Dietary protein, especially whey proteins (WP), may lower PPL. We hypothesised that a WP pre-meal (17·6 g protein) consumed 15 v.

Consumption of Whey in Combination with Dairy Medium-Chain Fatty Acids (MCFAs) may Reduce Lipid Storage due to Urinary Loss of Tricarboxylic Acid Cycle Intermediates and Increased Rates of MCFAs Oxidation.

Scope: The aim of the paper is to investigate whether changes in the metabolome could explain observed changes in body composition in overweight adults after consumption of butter with high level of medium-chain fatty acids (MCFAs) in combination with casein or whey.

Methods And Results: With GC-TOF and LC-Q/MS, metabolites in plasma and urine from a 12-week randomized double-blinded human intervention including 52-abdominally overweight adults were analyzed. The participants consumed 63 g per day of milk fat (high or low in MCFAs) and 60 g per day of protein (whey or casein).

Whole Milk Increases Intestinal ANGPTL4 Expression and Excretion of Fatty Acids through Feces and Urine.

The angiopoietin-like 4 (ANGPLT4) protein is involved in lipid metabolism and is known to inhibit lipoprotein lipase in the bloodstream. We investigated the effect of milk on intestinal ANGPTL4 and the metabolic profile of growing pigs and the effect of free fatty acids (FFAs) on ANGPTL4 in ex vivo and in vitro assays. Feeding pigs whole milk increased intestinal ANGPTL4 mRNA and increased fecal excretion of long-chain FFA compared to the control group fed soybean oil (n = 9).

Direct Derivatization vs Aqueous Extraction Methods of Fecal Free Fatty Acids for GC-MS Analysis.

A comprehensive and accurate determination of free fatty acids (FFA) is required for fecal metabolomic investigations. The present study compares three aqueous extraction methods (1) ULTRA-TURRAX(®), (2) whirl mixing and (3) basic ULTRA-TURRAX extraction of fecal FFA with a direct derivatization approach using ethyl chloroformate as the derivatization reagent before determination by gas chromatography-mass spectrometry. The direct derivatization method resulted in significantly higher estimations (P < 0.

Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study.

Background: Abdominal obesity and exaggerated postprandial lipemia are independent risk factors for cardiovascular disease (CVD) and mortality, and both are affected by dietary behavior.

Objective: We investigated whether dietary supplementation with whey protein and medium-chain saturated fatty acids (MC-SFAs) improved postprandial lipid metabolism in humans with abdominal obesity.

Design: We conducted a 12-wk, randomized, double-blinded, diet intervention study.

Novel GHB-derived natural products from European mistletoe (Viscum album).

Context: The European white-berry mistletoe [Viscum album L. (Loranthaceae)] is among the oldest known medicinal plants. At present the most important application of mistletoe extracts is in the treatment of cancer.