Discovery of a series of portimine-A fatty acid esters in mussels.

Vulcanodinium rugosum is a benthic dinoflagellate known for producing pinnatoxins, pteriatoxins, portimines and kabirimine. In this study, we aimed to identify unknown analogs of these emerging toxins in mussels collected in the Ingril lagoon, France. First, untargeted data acquisitions were conducted by means of liquid chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Data processing involved a molecular networking approach, and a workflow dedicated to the identification of biotransformed metabolites. Additionally, targeted analyses by liquid chromatography coupled to triple quadrupole mass spectrometry were also implemented to further investigate and confirm the identification of new compounds. For the first time, a series of 13-O-acyl esters of portimine-A (n = 13) were identified, with fatty acid chains ranging between C12:0 and C22:6. The profile was dominated by the palmitic acid conjugation. This discovery was supported by fractionation experiments combined with the implementation of a hydrolysis reaction, providing further evidence of the metabolite identities. Furthermore, several analogs were semi-synthesized, definitively confirming the discovery of these metabolization products. A new analog of pinnatoxin, with a molecular formula of C42H65NO9, was also identified across the year 2018, with the highest concentration observed in August (4.5 µg/kg). The MS/MS data collected for this compound exhibited strong structural similarities with PnTX-A and PnTX-G, likely indicating a substituent C2H5O2 in the side chain at C33. The discovery of these new analogs will contribute to deeper knowledge of the chemodiversity of toxins produced by V. rugosum or resulting from shellfish metabolism, thereby improving our ability to characterize the risks associated with these emerging toxins.

Differential responses of rumen and fecal fermentation and microbiota of Liaoning cashmere goats after 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester supplementation.

The 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi), a rumen protective methionine, has been extensively studied in dairy cows and beef cattle and has been shown to regulate gastrointestinal microbiota and improve production performance. However, knowledge of the application of HMBi on cashmere goats and the simultaneous study of rumen and hindgut microbiota is still limited. In this study, HMBi supplementation increased the concentration of total serum protein, the production of microbial protein in the rumen and feces, as well as butyrate production in the feces. The results of PCoA and PERMANOVA showed no significant difference between the rumen microbiota, but there was a dramatic difference between the fecal microbiota of the two groups of Cashmere goats after the HMBi supplementation. Specifically, in the rumen, HMBi significantly increased the relative abundance of some fiber-degrading bacteria (such as Fibrobacter) compared with the CON group. In the feces, as well as a similar effect as in the rumen (increasing the relative abundance of some fiber-degrading bacteria, such as Lachnospiraceae FCS020 group and ASV32), HMBi diets also increased the proliferation of butyrate-producing bacteria (including Oscillospiraceae UCG-005 and Christensenellaceae R-7 group). Overall, these results demonstrated that HMBi could regulate the rumen and fecal microbial composition of Liaoning cashmere goats and benefit the host.

Analysis of ester-producing performance in high-yield ethyl hexanoate yeast and the effect on metabolites in bio- enhanced Daqu, the starter for Baijiu and other traditional fermented foods.

AIMS: Ethyl hexanoate, one of the key flavor compounds in strong-flavor Baijiu. To improve the content of ethyl hexanoate in strong-flavor Baijiu, a functional strain with high yield of ethyl hexanoate was screened and its ester-producing performance was studied. METHODS AND RESULTS: Upon identification, the strain was classified as Candida sp. and designated as ZY002. Under optimal fermentation conditions, the content of ethyl hexanoate synthesized by ZY002 can be as high as 170.56 mg L-1. A fermentation test was carried out using the ZY002 strain bioaugmented Daqu to verify the role of the strain applied to Baijiu brewing. It was found that strain ZY002 could not only improve the moisture and alcohol contents of fermented grains but also diminish the presence of reducing sugar and crude starch. Furthermore, it notably amplified the abundance of flavor compounds. CONCLUSION: In this study, Candida sp. ZY002 with a high yield of ethyl hexanoate provided high-quality strain resources for the actual industrial production of Baijiu.

Gender-specific abdominal fat distribution and insulin resistance associated with organophosphate esters and phthalate metabolites exposure.

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

The dissipation of organophosphate esters mediated by ryegrass root exudate oxalic acid in soil: Analysis of enzymes activities, microorganism.

Complex rhizoremediation is the main mechanism of phytoremediation in organic-contaminated soil. Low molecular weight organic acids (LMWOAs) in root exudates have been shown to increase the bioavailability of contaminants and are essential for promoting the dissipation of contaminants. The effects of root exudates on the dissipation of organophosphate esters (OPEs) in soil are unclear. Consequently, we studied the combined effects of root exudates, soil enzymes and microorganisms on OPEs (tri (1-chloro-2-propyl) phosphate (TCPP) and triphenyl phosphate (TPP)) dissipation through pot experiments. Oxalic acid (OA) was confirmed to be the main component of LMWOAs in root exudates of ryegrass. The existence of OA increased the dissipation rate of OPEs by 6.04%-25.50%. Catalase and dehydrogenase activities were firstly activated and then inhibited in soil. While, urease activity was activated and alkaline phosphatase activity was inhibited during the exposure period. More bacteria enrichment (e.g., Sphingomonas, Pseudomonas, Flavisolibacter, Pontibacter, Methylophilus and Massilia) improved the biodegradation of OPEs. In addition, the transformation paths of OPEs hydrolysis and methylation under the action of root exudates were observed. This study provided theoretical insights into reducing the pollution risk of OPEs in the soil.

Protective effect of sucrose esters from cape gooseberry (Physalis peruviana L.) in TNBS-induced colitis.

Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Biodegradation of phthalate acid esters and whole-genome analysis of a novel Streptomyces sp. FZ201 isolated from natural habitats.

Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.

Classification, biosynthesis, and biological functions of triterpene esters in plants.

Triterpene esters comprise a class of secondary metabolites that are synthesized by decorating triterpene skeletons with a series of oxidation, glycosylation, and acylation modifications. Many triterpene esters with important bioactivities have been isolated and identified, including those with applications in the pesticide, pharmaceutical, and cosmetic industries. They also play essential roles in plant defense against pests, diseases, physical damage (as part of the cuticle), and regulation of root microorganisms. However, there has been no recent summary of the biosynthetic pathways and biological functions of plant triterpene esters. Here, we classify triterpene esters into five categories based on their skeletons and find that C-3 oxidation may have a significant effect on triterpenoid acylation. Fatty acid and aromatic moieties are common ligands present in triterpene esters. We further analyze triterpene ester synthesis-related acyltransferases (TEsACTs) in the triterpene biosynthetic pathway. Using an evolutionary classification of BAHD acyltransferases (BAHD-ATs) and serine carboxypeptidase-like acyltransferases (SCPL-ATs) in Arabidopsis thaliana and Oryza sativa, we classify 18 TEsACTs with identified functions from 11 species. All the triterpene-skeleton-related TEsACTs belong to BAHD-AT clades IIIa and I, and the only identified TEsACT from the SCPL-AT family belongs to the CP-I subfamily. This comprehensive review of the biosynthetic pathways and bioactivities of triterpene esters provides a foundation for further study of their bioactivities and applications in industry, agricultural production, and human health.

Methylation of Phenyl Rings in Ester-Stabilized Phosphorus Ylides Vastly Enhances Their Protonophoric Activity.

We have recently discovered that ester-stabilized phosphorus ylides, resulting from deprotonation of a phosphonium salt such as [Ph3PCH2COOR], can transfer protons across artificial and biological membranes. To create more effective cationic protonophores, we synthesized similar phosphonium salts with one ((heptyloxycarbonylmethyl)(p-tolyl)bromide) or two ((butyloxycarbonylmethyl)(3,5-xylyl)osphonium bromide) methyl substituents in the phenyl groups. The methylation enormously augmented both protonophoric activity of the ylides on planar bilayer lipid membrane (BLM) and uncoupling of mammalian mitochondria, which correlated with strongly accelerated flip-flop of their cationic precursors across the BLM.

Uptake, translocation, and metabolism of organophosphate esters (OPEs) in plants and health perspective for human: A review.

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.

Effects of uptake pathways on the accumulation, translocation, and metabolism of OPEs in rice: An emphasis on foliar uptake.

The often-overlooked importance of foliar absorption on the plant uptake of organic pollutants was investigated by an exposure chamber test. Rice seedlings were exposed to organophosphate esters (OPEs) through 8 scenarios arranged from 3 major uptake pathways: root uptake via solution, foliar uptake via gas, and foliar uptake via particles, to identify the contributions of these 3 uptake pathways and their influences on the translocation and metabolism of OPEs in rice. The concentration of OPEs in rice tissues showed an "additive effect" with the increase of exposure pathways. OPEs in rice shoots mainly originated from foliar uptake through particle (29.6 %-63.5 %) and gaseous (28.5 %-49.4 %) absorptions rather than root uptake (7.86 %-24.2 %) under the exposure condition. In comparison with stomal absorption, wax layer penetration was the main pathway for most OPEs to enter into leaves, especially for those compounds with high octanol-air partition coefficients. Although the subcellular distributions of OPEs in the rice tissues of the foliar exposure were slightly different from those of the root exposure, hydrophobic OPEs were mainly stored in the cell wall with hydrophilic OPEs mainly in the cytosol. The translocation of OPEs from the exposed tissue to the unexposed tissue were significantly negatively correlated with their octanol-water partition coefficients, but their basipetal translocation were limited. The result suggested that the translocation of OPEs within rice is prioritized over their degradation. This study deepens our understanding of the processes behind OPE uptake by rice and highlights the importance of foliar uptake, especially for those via particle absorption.

Inoculation of Yarrowia lipolytica promotes the growth of lactic acid bacteria, Debaryomyces udenii and the formation of ethyl esters in sour meat.

Yarrowia lipolytica N12 and A13 with high lipase activity obtained by mutagenesis were inoculated into sour meat, and their effects on physicochemical properties, microbial community succession, free amino acids, and volatile compounds of sour meat were investigated. Inoculation fermentation increased the contents of free amino acids observably, rapidly reduced pH, promoted the accumulation of total acids, decreased 2-thiobarbituric acid reactive substances (TBARS) values. In addition, the addition of Y. lipolytica might contribute to the growth of lactic acid bacteria, Candida spp., and Debaryomyces udenii, which play an important role in production of volatile compounds. It was shown that inoculation promoted the production of esters, aldehydes, and alcohols, especially ethyl esters, giving sour meat a better meat flavor. Besides, it was found that Y. lipolytica A13 had better fermenting property. Sample of A13 group had higher contents of ethyl esters, free amino acids and dominant microorganisms. The results may help to provide new strains for sour meat fermentation.

Impact of Saccharomyces cerevisiae yeast inoculation mode on wine composition.

Inoculation modes are known to affect yeast behavior. Here, we characterized the impact of ADY and pre-culturing on the composition of the resulting wine, fermented by four commercial strains of Saccharomyces cerevisiae. Classical oenological parameters were not affected by the yeast inoculation mode. Using an untargeted metabolomic approach, a significant distinction in wine composition was noted regardless of the strain between the two inoculation modes, each associated with a specific metabolomic signature. 218 and 895 biomarkers were annotated, respectively, for ADYs associated with the preservation of wine polyphenols, and for pre-cultures related to the modulation of yeast nitrogen metabolism. Volatilome analysis revealed that the ester family was that most impacted by the inoculation mode whatever the strain. Ester production was enhanced in ADY condition. For the first time, the complete reprogramming of the yeast metabolism was revealed as a function of yeast preparation, which significantly impacts its volatilome and exometabolome.

Unravelling bioaccumulation, depletion and metabolism of organophosphate triesters in laying hens: Insight of in vivo biotransformation assisted by diester metabolites.

Organophosphate triesters (tri-OPEs) threaten human health through dietary exposure, but little is known about their feed-to-food transfer and in vivo behavior in farm animals. Herein 135 laying hens were fed with contaminated feed (control group, low-level group and high-level group) to elucidate the bioaccumulation, distribution, and metabolism of the six most commonly reported tri-OPEs. The storage (breast muscle), metabolism and mobilization (liver and blood) and non-invasive (feather) tissues were collected. The exposure-increase (D1∼14) and depuration-decrease (D15∼42) trends indicated that feed exposure caused tri-OPE accumulation in animal tissues. Tissue-specific and moiety-specific behavior was observed for tri-OPEs. The highest transfer factor (TF) and transfer rate (TR) were observed in liver (TF: 14.8%∼82.3%; TR: 4.40%∼24.5%), followed by feather, breast muscle, and blood. Tris(2-chloroisopropyl) phosphate (TCIPP) had the longest half-life in feather (72.2 days), while triphenyl phosphate (TPhP) showed the shortest half-life in liver (0.41 days). Tri-OPEs' major metabolites (organophosphate diesters, di-OPEs) were simultaneously studied, which exhibited dose-dependent and time-dependent variations following administration. In breast muscle, the inclusion of di-OPEs resulted in TF increases of 735%, 1108%, 798%, and 286% than considering TCIPP, tributyl phosphate, tris(2-butoxyethyl) phosphate and tris(2-ethylhexyl) phosphate alone. Feather was more of a proxy of birds' long-term exposure to tri-OPEs, while short-term exposure was better reflected by di-OPEs. Both experimental and in silico modeling methods validated aryl-functional group facilitated the initial accumulation and metabolism of TPhP in the avian liver compared to other moiety-substituted tri-OPEs.

Uptake mechanism, translocation, and transformation of organophosphate esters in water hyacinth (Eichhornia crassipes): A hydroponic study.

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.

Engineering a Synthetic Escherichia coli Coculture for Compartmentalized de novo Biosynthesis of Isobutyl Butyrate from Mixed Sugars.

Short-chain esters are versatile chemicals that can be used as flavors, fragrances, solvents, and fuels. The de novo ester biosynthesis consists of diverging and converging pathway submodules, which is challenging to engineer to achieve optimal metabolic fluxes and selective product synthesis. Compartmentalizing the pathway submodules into specialist cells that facilitate pathway modularization and labor division is a promising solution. Here, we engineered a synthetic Escherichia coli coculture with the compartmentalized sugar utilization and ester biosynthesis pathways to produce isobutyl butyrate from a mixture of glucose and xylose. To compartmentalize the sugar-utilizing pathway submodules, we engineered a xylose-utilizing E. coli specialist that selectively consumes xylose over glucose and bypasses carbon catabolite repression (CCR) while leveraging the native CCR machinery to activate a glucose-utilizing E. coli specialist. We found that the compartmentalization of sugar catabolism enabled simultaneous co-utilization of glucose and xylose by a coculture of the two E. coli specialists, improving the stability of the coculture population. Next, we modularized the isobutyl butyrate pathway into the isobutanol, butyl-CoA, and ester condensation submodules, where we distributed the isobutanol submodule to the glucose-utilizing specialist and the other submodules to the xylose-utilizing specialist. Upon compartmentalization of the isobutyl butyrate pathway submodules into these sugar-utilizing specialist cells, a robust synthetic coculture was engineered to selectively produce isobutyl butyrate, reduce the biosynthesis of unwanted ester byproducts, and improve the production titer as compared to the monoculture.

Structural characterization of a nonionic rhamnolipid from Burkholderia lata.

We present the isolation and structural characterization of a novel nonionic dirhamnolipid methyl ester produced by the bacterium Burkholderia lata. The structure and the absolute configuration of the isolated dirhamnolipid bearing a symmetrical C14-C14 methyl ester chain were thoroughly investigated through chemical degradation and spectroscopic methods including 1D and 2D NMR analysis, HR-ESI-TOF-MS, chiral GC-MS, and polarimetry. Our work represents the first mention in the literature of a rhamnolipid methyl ester from Burkholderia species.

Reverse metabolomics for the discovery of chemical structures from humans.

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.

Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network.

With the widespread use of organophosphate esters (OPEs), the accumulation and toxicity effect of OPEs in biota are attracting more and more concern. In order to clarify the mechanism of toxicity of OPEs to organisms, this study reviewed the OPEs toxicity and systematically identified the mechanism of OPEs toxicity under the framework of adverse outcome pathway (AOP). OPEs were divided into three groups (alkyl-OPEs, aryl-OPEs, and halogenated-OPEs) and biota was divided into aquatic organism and mammals. The results showed that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) mainly caused neurotoxicity, reproductive, and hepatotoxicity in different mechanisms. According to the constructed AOP network, the toxicity mechanism of OPEs on aquatic organisms and mammals is different, which is mainly attributed to the different biological metabolic systems of aquatic organisms and mammals. Interestingly, our results indicate that the toxicity effect of the three kinds of OPEs on aquatic organisms is different, while there was no obvious difference in the mechanism of toxicity of OPEs on mammals. This study provides a theoretical basis for OPEs risk assessment in the future.