Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and in vitro experiments.

5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through in vitro experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in In vitro experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.

5-HMF attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis mice by inhibiting the MIF-CD74 interaction.

The neuroprotective role of 5-hydroxymethyl-2-furfural (5-HMF) has been demonstrated in a variety of neurological diseases. The aim of this study is to investigate the effect of 5-HMF on multiple sclerosis (MS). IFN-γ-stimulated murine microglia (BV2 cells) are considered a cell model of MS. With 5-HMF treatment, microglial M1/2 polarization and cytokine levels are detected. The interaction of 5-HMF with migration inhibitory factor (MIF) is predicted using online databases. The experimental autoimmune encephalomyelitis (EAE) mouse model is established, followed by a 5-HMF injection. The results show that 5-HMF facilitates IFN-γ-stimulated microglial M2 polarization and attenuates the inflammatory response. According to the network pharmacology and molecular docking results, 5-HMF has a binding site for MIF. Further results show that blocking MIF activity or silencing CD74 enhances microglial M2 polarization, reduces inflammatory activity, and prevents ERK1/2 phosphorylation. 5-HMF inhibits the MIF-CD74 interaction by binding to MIF, thereby inhibiting microglial M1 polarization and enhancing the anti-inflammatory response. 5-HMF ameliorates EAE, inflammation, and demyelination in vivo. In conclusion, our research indicates that 5-HMF promotes microglial M2 polarization by inhibiting the MIF-CD74 interaction, thereby attenuating inflammation and demyelination in EAE mice.

Voltammetric Determination of 5-Hydroxymethyl-2-furfural in Processed Cheese Using an Easy-Made and Economic Integrated 3D Graphene-like Electrode.

The concentration of 5-hydroxymethyl-2-furfural (HMF) is an important quality-related index in milk and milk products. Fast, cost-effective and environmentally friendly determination of HMF is of great significance in milk products control. In this study, a three-dimensional (3D) graphene-like surface (3DGrls) was successfully prepared within 5 min by an electrochemical amperometric pretreatment on a pencil graphite electrode (PGE). The fast-obtained 3D graphene-like surface increased the electrode surface area and enhanced the electron transfer capability without the addition of any harmful chemicals. The morphology and chemical composition of the obtained electrode were characterized by scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). The results found that the electrochemical response to HMF at the prepared 3DGrls/PGE was 34 times higher than that at PGE. The modified electrode showed a good linear response to HMF in a concentration range of 0.35~116 µM with a low limit of detection (LOD) of 0.099 µM. The integrated electrode also exhibited excellent stability and wonderful antifouling property. Furthermore, the 3DGrls/PGE was successfully applied for the determination of HMF in three processed cheese samples with satisfactory results.

Co-Extraction and Co-Purification Coupled with HPLC-DAD for Simultaneous Detection of Acrylamide and 5-hydroxymethyl-2-furfural in Thermally Processed Foods.

Acrylamide and 5-hydroxymethyl-2-furfural (5-HMF) are two of the most abundant compounds generated during thermal processing. A simple method for the simultaneous quantitation of acrylamide and 5-HMF was developed and successfully applied in thermally processed foods. Acrylamide and 5-HMF were co-extracted with methanol and then purified and enriched by an Oasis HLB solid-phase extraction cartridge, simultaneously analyzed by high-performance liquid chromatography and detected with a diode array detector, respectively, at their optimal wavelength. The linear concentration range was found to be 25-5000 µg/L with high linear correlation coefficients (R > 0.999). The limit of detection and the limit of quantitation for acrylamide and 5-HMF were 6.90 µg/L and 4.66 µg/L, and 20.90 µg/L and 14.12 µg/L, respectively. The recovery of acrylamide and 5-HMF in biscuits, bread, Chinese doughnuts, breakfast cereals, and milk-based baby foods was achieved at 87.72-96.70% and 85.68-96.17% with RSD at 0.78-3.35% and 0.55-2.81%, respectively. The established method presents simplicity, accuracy and good repeatability, and can be used for the rapid simultaneous quantitation of acrylamide and 5-HMF in thermally processed foods.

Conversion of D-fructose to 5-acetoxymethyl-2-furfural Using Immobilized Lipase and Cation Exchange Resin.

5-Acetoxymethyl-2-furfural (AMF) was prepared from D-fructose via 1,6-diacetylfructose (DAF) through a simple two-step reaction pathway. Immobilized enzyme (Novozym 435) was found to be the best enzymatic catalyst for the trans-esterification step (yielding 94.6% DAF). In the dehydration step, while soluble H2SO4 was found to be the best acidic catalyst (yielding 86.6% AMF), we opted to utilize heterogeneous cation exchange resin (Amberlyst 15) together with recyclable industrial solvents (1,4-dioxane) for a more sustainable AMF synthesis procedure. Although the total yield of AMF was a little lower, both the enzyme and the solid acid catalyst could be recycled for five cycles without a significant loss of activity, which has a major contribution to the cost-efficient aspect of the entire process.

Formation and Alterations of the Potentially Harmful Maillard Reaction Products during the Production and Storage of Brown Fermented Milk.

To improve the quality and safety of brown fermented milk (BFM), the formation and alterations of potentially harmful Maillard reaction products (MRPs), including 3-deoxyglucosone (3-DG), methylglyoxal (MGO), 5-(hydroxymethyl)-2-furfural (HMF), acrylamide and flavour components were investigated during the browning, fermentation and commercial storage. MRPs were shown to be produced mainly during the browning stage. The levels of different substances varied during the fermentation and commercial storage stage. The proportion and type of carboxylic acids in the flavour components significantly increased during the fermentation stage. Browning index of milk during the browning stage was shown to be positively associated with the 3-DG (Pearson's r = 0.9632), MGO (Pearson's r = 0.9915), HMF (Pearson's r = 0.9772), and acrylamide (Pearson's r = 0.7910) levels and the total percentage of the flavour components from four different categories (Pearson's r = 0.7407). Changes in physicochemical properties of BFM during production not only contribute to predict the formation of potentially unhealthy MRPs, but also Lactobacillus species used for the fermentation should be carefully selected to improve the quality of this product.

Computational study on the Maillard reactions of glucose and galactose with lysine.

CONTEXT: Milk has nutrient-rich but thermal sensitive matrix that undergoes varying degrees of Maillard reaction (MR) at heating conditions. The MR mainly occurs between lysine residues (Lys) and lactose composed of glucose (Glc) and galactose (Gal), which are abundantly sourced from dairy products. In the present study, the MRs of Glc and Gal with Lys at the initial and intermediate stages have been investigated theoretically using density functional theory (DFT) to simulate the gaseous and aqueous phases. Reaction mechanisms have been proposed, and relative energy changes of different steps were calculated according to the total mass balance. The calculations reveal that both Nα- and Nε-amine groups of Lys can react with the carbonyl functional group of Glc and Gal with the similar potential energy profiles, and Gal is more reactive than Glc. However, the barrier in Nε-channel is lower than in Nα-channel, indicating a faster reaction rate through the former channel compared with the latter. The 5-hydroxymethyl-2-furfural (HMF) and derivative are formed under 3-deoxysone route in the intermediate stage. The calculation results are helpful for proposing a reasonable MR mechanism and suggesting possible control methods of the MRs. METHODS: In this study, different levels of DFT calculations have been conducted to investigate the mechanisms and favorability of generating MR products in Glc-Lys and Gal-Lys models at initial and intermediate stages in the gaseous and aqueous conditions. In order to elucidate the molecular models from the perspectives of chemistry and geometry, DFT calculations were performed by the mean of B3LYP functional at basis sets of 6-311 + + G (d, p) and 6-311 + + G (2df, 2p) with optional solvation settings. To examine the solvation effect, the study further constructed models with solvent H2O and calculated in wB97XD functional with 6-31 + G (d) basis set. All computations were carried out Gaussian 09 suite of quantum chemistry software.

Towards a better understanding of light-glucose induced modifications on the structure and biological activity of formulated Nivolumab.

In the last years, monoclonal antibodies (mAbs) have rapidly escalated as biopharmaceuticals into cancer treatments, mainly for their target specificity accompanied by less side effects than the traditional chemotherapy, and stimulation of reliable long-term anti-tumoral responses. They are potentially unstable macromolecules under shaking, temperature fluctuations, humidity, and indoor and outdoor light exposure, all stressors occurring throughout their production, transport, storage, handling, and administration steps. The chemical and physical modifications of mAbs can lead not only to the loss of their bioactivity, but also to the enhancement of their immunogenicity with increasing risk of severe hypersensitivity reactions in treated patients because of aggregation. The photostability of Nivolumab, the active principle of Opdivo®, has been here studied. The chemical modifications detected by LC-MS/MS after the light stressor showed Trp and Met mono and double oxidations as primary damage induced by light on this mAb. The oxidations were stronger when the mAb was diluted in sterile glucose solution where 5-HMF, a major heat glucose degradation product, acted as singlet oxygen producer under irradiation. However, no significant changes in the mAb conformation were found. On the contrary, formation of a significant extent of aggregates has been detected after shining high simulated sunlight doses. This again took place particularly when Nivolumab was diluted in sterile glucose, thus raising a direct correlation between the aggregation and the oxidative processes. Finally, the biological activity under light stress assessed by a blockade assay test demonstrated the maintenance of the PD-1 target recognition even under high light doses and in glucose solution, in line with the preservation of the secondary and tertiary structures of the mAb. Based on our results, as sterile glucose is mostly used for children's therapies, special warnings, and precautions for healthcare professionals should be included for their use to the pediatric population.

Improving fried burger quality and modulating acrylamide formation by active coating containing Rosa canina L. extract nanoemulsions.

During the frying of foods, undesirable reactions such as protein denaturation, acrylamide formation, and so on occur in the product, which has confirmed carcinogenic effects. The use of antioxidants has been proposed as an effective solution to reduce the formation of these compounds during the process. The current study aimed to assess the impact of an edible coating holding within chia seed gum (CSG) and Rosa canina L. extract (RCE) nanoemulsions on the physicochemical properties, oil uptake, acrylamide formation, 5-hydroxymethyl-2-furfural (HMF) content, and sensory characteristics of beef-turkey burgers. The RCE-loaded nanoemulsions were prepared using the ultrasonic homogenization method, and different concentrations (i.e., 10%, 20%, and 40% w/w) were added to the CSG solutions; these active coatings were used to cover the burgers. CSG-based coatings, especially coatings containing the highest concentration of nanoemulsions (40%), caused a significant decrease in the oil uptake and moisture retention, acrylamide content, and HMF content of fried burgers. The texture of coated burgers was softer than that of uncoated samples; they also had a higher color brightness and a lower browning index. Field emission scanning electron microscopy analysis showed that RCE concentration less than 40% should be used in CSG coatings because it will cause minor cracks, which is an obvious possibility of failure of coating performance. Coating significantly (4-10 times) increased the antioxidant activity of burgers compared to the control. In conclusion, it is suggested to use the active coating produced in this study to improve fried burger quality and modulate acrylamide formation.

Indirect competitive ELISA based on monoclonal antibody for the detection of 5-hydroxymethyl-2-furfural in milk, compared with HPLC.

In this study, a method for rapid detection of 5-hydroxymethyl-2-furfural (HMF) was investigated. Monoclonal antibody (anti-HMF) was prepared and evaluated by an indirect competitive ELISA (ic-ELISA) format. The optimized standard curve was y=-0.2097x+1.0432 [where x is the logarithm (base 10) of the values of the HMF concentration and y is the absorbance of ic-ELISA results tested at 490 nm] and the linear detection range was 0.008 to 32.768 mg/L. The percentage of cross-reactivity of HMF with 5 major furfural derivatives was less than 2.92%. Finally, the established ic-ELISA format was used to test HMF in milk, and compared with the result obtained by HPLC, which produced an error of about 0.3%. Based on the data in this experiment, we concluded that the established ic-ELISA format was reliable with a high specificity.

The antioxidant and antiglycation activities of selected spices and other edible plant materials and their decay in sugar-protein systems under thermal stress.

Antiglycation activities of herbs and spices, have been described in relation to their in vivo anti-diabetic or anti-aging activity at physiological temperature. Under the hypothesis that those natural antioxidants may inhibit the formation of Maillard intermediates, the behavior of several hydroalcoholic plant extracts was analyzed in sugar-protein systems. Allspice, thyme, green pepper and black pepper extracts were the most efficient inhibitors, decreasing furosine formation by 60, 45, 40 and 30%, respectively. 5-hydroxymethyl-2-furfural formation decreased in the presence of the extracts and protein glycation was inhibited by the thyme extract in advanced stages. Antiglycation activities were related to polyphenols content, to radical scavenging and to iron-reducing power. In the protein-sugar systems studied at the time in which 4000 ppm of furosine were formed, the antioxidant activity dropped between 30 and 40%. Polyphenols inhibit Maillard intermediates formation, revealing the incidence of oxidative pathways, but they are depleted as a function of time.

Formation and Identification of a 5-(Hydroxymethyl)-2-Furfural-Zingerone Condensate and Its Cytotoxicity in Caco-2 Cells.

5-(Hydroxymethyl)-2-furfural (HMF), an active furfural, widely exists in various food products and has potential safety risks. It can be eliminated by occurring aldol condensation with α-unsubstituted ketones in the presence of catalysts. However, the elimination process between HMF and ketones from food is rarely studied. In this study, the adduct formation between HMF and zingerone (ZGR) catalyzed by proline was investigated. It revealed that the adduct formation led to 99.75% of HMF being trapped under the optimized reaction condition. Moreover, the in vitro digestion stability of HMF-ZGR adduct (HMZ) and its cytotoxicity against Caco-2 cells were evaluated. The results indicated that more than 75% of HMZ was remained after a three-stage simulated digestion. Following 24 and 48 h of incubation, HMZ exhibited cytotoxicity against Caco-2 cells with IC50 values of 41.47 ± 5.33 and 25.39 ± 3.12 mM, respectively, versus 35.39 ± 4.03 and 19.17 ± 2.10 mM by HMF.

Determination of 5-hydroxymethylfurfural using an electropolymerized molecularly imprinted polymer in combination with Salle.

Coffee, a beverage with a complex chemical composition, is appreciated for the sensory experience of its taste and aroma. The compound 5-(hydroxymethyl)-2-furfural (HMF) is essential for sensory characterization of the beverage, and is also used in the traceability of its production. In this work, a procedure combining salting-out assisted liquid-liquid extraction (SALLE) and an electropolymerized molecularly imprinted polymer (e-MIP) was developed for the detection and quantification of HMF in coffee samples. The sample preparation step using SALLE employed a combination of acetonitrile and phosphate-buffered saline, in a proportion of 70:30 (ACN:PBS), with addition of 0.02 g of NaCl. The new sensor (e-MIP) was prepared by electropolymerization of p-aminobenzoic acid onto a glassy carbon electrode (GCE) using cyclic voltammetry (CV). Analytical determinations were performed by differential pulse voltammetry (DPV). The linear regression correlation coefficient (r2) for the response was 0.9986. The limits of detection and quantification were 0.372 mg L-1 and 1.240 mg L-1, respectively. The repeatability and reproducibility values obtained were 6 and 10%, respectively. The recoveries for three concentration levels were between 97 and 101%. Analyses of different coffee samples showed that the HMF concentrations varied from 261.0 ± 41.0 to 770.2 ± 55.9 mg kg-1 in powdered coffee samples, and from 1510 ± 50 to 4445 ± 278 mg kg-1 in instant coffee samples. The advantages of this procedure, compared to other methods described in the literature, are its simplicity, easy operation, good selectivity and sensitivity, low cost, and minimal use of organic solvents.

A novel UHPLC method for determining the degree of coffee roasting by analysis of furans.

The aim of this study was to develop a multi-analyte UHPLC method for furans and to apply it to commercial coffee samples as well as commercial roasting trials. Furans, as rising time-temperature indicators (TTIs), promised to be an alternative to unsatisfactory roasting temperature measurements. Consequently, a UHPLC-UV method for the determination of 5-hydroxymethyl-2-furfural (HMF), 5-hydroxymethyl-2-furoic acid (HMFA), 2-furfural (F), 5-methylfurfural (MF), 2-furyl methyl ketone (FMC), 2-furoic acid (FA), and for 3-caffeoylquinic acid (3-CQA) was developed and validated. Commercial roasted coffee beans contained 77.7-322 mg/kg HMF, 73.3-158 mg/kg HMFA, 109-200 mg/kg 2-F, 157-209 mg/kg MF, 12.3-32.8 mg/kg FMC, and 137-205 mg/kg FA. Roasting trial samples showed strong rising HMF contents (max.: Arabica: 769 mg/kg, Robusta: 364 mg/kg) followed by a distinct decline. Only MF and FA appeared as steady rising TTIs in the roasting process in Arabica and Robusta beans. 3-CQA fitted well as a decreasing TTI as expected.

5-Hydroxymethyl-2-Furfural Oxidation Over Au/CexZr1-xO2 Catalysts.

A series of gold catalysts supported on pure CeO2, ZrO2, and two different Ce-Zr mixed oxides have been prepared and tested in the 5-hydroxymethyl-2-furfural oxidation reaction. All catalysts show high catalytic activity (100% conversion) and important selectivity (27-41%) to the desired product i.e., 2,5-furandicarboxylic acid at low base concentration. Products selectivity changes with the support nature as expected, however, the observed trend cannot be related neither to gold particle size, nor to catalyst reducibility and oxygen mobility. An important relation between the FDCA selectivity and the support textural properties is observed, conducing to the general requirement for optimal pore size for this reaction.

Changes of 5-hydroxymethyl-2-furfural in fresh and processed ginsengs.

The study estimated changes of 5-hydroxymethyl-2-furfuraldehyde (5-HMF) in different ginseng products with different temperatures and time pretreatment. Heat treatment was performed at various temperatures for 1.50, 2.00, 2.50, and 3.00 hr, respectively. Ultrasonic extraction and reflux extraction were used to evaluate the extraction rate and different solvents (such as 80% methanol, dichloromethane, ethyl acetate, and an extraction with both dichloromethane and ethyl acetate solvents) using two extraction methods (liquid-liquid extraction and solid-phase extraction) to remove matrix interference. An ultraperformance liquid chromatography-mass spectrometer (UPLC-MS) method was used for quantitative and changing analysis of 5-HMF in different ginseng samples. The results indicated that the content of 5-HMF increased dramatically with heating temperature and time, and the 5-HMF in the ginseng samples ranged from 0.01 to 112.32 g/kg protein. The highest value was observed in the honey-added ginseng samples with the highest amount of addition and highest temperature treatment, and the lowest value was found in the fresh ginseng samples. These results implied that 5-HMF may be as an indicator to estimate the honey addition level and heat treatment degree during the processing of ginseng products, and the content of 5-HMF is a promising parameter to evaluate the quality of products (ginseng). The production and regulation of potentially harmful Maillard reaction products (PHMRPs)-5-HMF in ginseng manufacture will provide an important reference for safe ginseng processing.

5-Hydroxymethylfurfural accumulation plays a critical role on acrylamide formation in coffee during roasting as confirmed by multiresponse kinetic modelling.

This study aims to investigate in depth the mechanism of acrylamide formation in coffee during roasting. For this purpose, a comprehensive kinetic model including the elementary steps for acrylamide formation was proposed. The changes in sucrose, reducing sugars, free amino acids, asparagine, acrylamide, 3-deoxyglucosone, methylglyoxal, glyoxal, and 5-hydroxymethylfurfural were monitored in coffee during roasting at 200, 220 and 240 °C. Dominant pathways of complex reactions leading to acrylamide were unravelled by means of multiresponse kinetic modelling approach. The results of the model indicated that sucrose degrades into glucose and a reactive fructofuranosyl cation. Interestingly, glucose takes part mostly in the formation of intermediates, glyoxal and especially 3-deoxyglucosone rather than acrylamide formation. On the other hand, fructofuranosyl cation contributed mostly to the formation of 5-hydroxymethylfurfural which was found to be the most important intermediate precursor of acrylamide formed in coffee during roasting.

Antioxidant and anti-glycation potential of green pepper (Piper nigrum): Optimization of ß-cyclodextrin-based extraction by response surface methodology.

Green pepper (Piper nigrum) presents high levels of functional compounds, with antioxidant and anti-glycation properties. Thus, the optimization of the ß-cyclodextrin-based extraction of functional compounds from green pepper through Response Surface Methodology was performed. The optimum extraction conditions were assessed by optimizing total polyphenolic content (TPC) and antioxidant activity (DPPH• and FRAP methods). 15 mM for ß-CD solution, 5 min of ultrasonication and 41 °C were the optimum extraction conditions, with the TPC of 24.9 mg GAE/mL and the anti-radical activities were 3.1 mg GAE/mL (DPPH• assay) and 0.45 mg GAE/mL (FRAP method). This natural extract obtained through eco-friendly techniques proved to be effective to reduce the formation of hydroxymethylfurfural, a glycation marker, at 70 and 80 °C. GPE presented higher TPC than black and white pepper. The relationship between the antioxidant and anti-glycation properties was confirmed and green pepper and can be proposed as a natural potential anti-glycation agent.

Antisickling Drugs Targeting ßCys93 Reduce Iron Oxidation and Oxidative Changes in Sickle Cell Hemoglobin.

Sickle cell disease is a genetic blood disorder caused by a single point mutation in the ß globin gene where glutamic acid is replaced by valine at the sixth position of the ß chain of hemoglobin (Hb). At low oxygen tension, the polymerization of deoxyHbS into fibers occurs in red blood cells (RBCs) leading to an impaired blood vessel transit. Sickle cell hemoglobin (HbS), when oxidized with hydrogen peroxide (H2O2), stays longer in a highly oxidizing ferryl (Fe4+) form causing irreversible oxidation of ßCys93 to a destabilizing cysteic acid. We have previously reported that an antisickling drug can be designed to bind specifically to ßCys93 and effectively protect against its irreversible oxidation by H2O2. Here, we report oxygen dissociation, oxidation, and polymerization kinetic reactions for four antisickling drugs (under different preclinical/clinical developmental stages) that either site-specifically target ßCys93 or other sites on the HbS molecule. Molecules that specifically bind to or modify ßCys93, such as 4,4'-di(1,2,3-triazolyl) disulfide (TD-3) and hydroxyurea (HU) were contrasted with molecules that target other sites on Hb including 5-hydroxymethyl-2-furfural (5-HMF) and L-glutamine. All reagents induced a left shift in the oxygen dissociation curve (ODC) except L-glutamine. In the presence of H2O2 (2.5:1, H2O2:heme), both TD-3 and HU reduced the ferryl heme by 22 and 37%, respectively, which corresponded to a 3- to 2-fold reduction in the levels of ßCys93 oxidation as verified by mass spectrometry. Increases in the delay times prior to polymerization of HbS under hypoxia were in the following order: TD-3 > HU > 5-HMF = L-glutamine. Designing antisickling agents that can specifically target ßCys93 may provide a dual antioxidant and antisickling therapeutic benefits in treating this disease.

Expression of a heat-stable NADPH-dependent alcohol dehydrogenase from Thermoanaerobacter pseudethanolicus 39E in Clostridium thermocellum 1313 results in increased hydroxymethylfurfural resistance.

BACKGROUND: Resistance to deconstruction is a major limitation to the use of lignocellulosic biomass as a substrate for the production of fuels and chemicals. Consolidated bioprocessing (CBP), the use of microbes for the simultaneous hydrolysis of lignocellulose into soluble sugars and fermentation of the resulting sugars to products of interest, is a potential solution to this obstacle. The pretreatment of plant biomass, however, releases compounds that are inhibitory to the growth of microbes used for CBP. RESULTS: Heterologous expression of the Thermoanaerobacter pseudethanolicus 39E bdhA gene, that encodes an alcohol dehydrogenase, in Clostridium thermocellum significantly increased resistance to furan derivatives at concentrations found in acid-pretreated biomass. The mechanism of detoxification of hydroxymethylfurfural was shown to be primarily reduction using NADPH as the cofactor. In addition, we report the construction of new expression vectors for homologous and heterologous expression in C. thermocellum. These vectors use regulatory signals from both C. bescii (the S-layer promoter) and C. thermocellum (the enolase promoter) shown to efficiently drive expression of the BdhA enzyme. CONCLUSIONS: Toxic compounds present in lignocellulose hydrolysates that inhibit cell growth and product formation are obstacles to the commercialization of fuels and chemicals from biomass. Expression of genes that reduce the effect of these inhibitors, such as furan derivatives, will serve to enable commercial processes using plant biomass for the production of fuels and chemicals.