Substrate Concentration Research Articles

High nitrogen removal and electricity generation of anaerobic fluidized bed coupled microbial fuel cell for Anammox

The current challenge in wastewater denitrification lies in the treatment of low carbon to nitrogen ratio(C/N) wastewater. Integrating Anaerobic Ammonia Oxidation(Anammox) with a microbial fuel cell(MFC) enables simultaneous pollutant removal and electricity generation, leading to enhanced treatment efficiency and reduced energy consumption. However, achieving stable and effective treatment effects under high nitrogen concentration conditions remains a general research difficulty. The Anaerobic fluidized bed MFC(AFB-MFC) experiment successfully integrated Anammox ammonia oxidizing bacteria (AnAOB) into the anode and cathode chambers, resulting in a continuous operation for 258 days. The reactor successfully initiated operation within 48 days and maintained stable performance within an NLR range of 0.5-1.0 kgN/m3/d. The system performance was found to be influenced by DO and substrate concentration, demonstrating consistent high nitrogen removal ability across different HRT. Ultimately, the Anammox AFB-MFC achieved a nitrogen removal efficiency (NRE) of 96.89%, while its power generation performance gradually improved, yielding a final output voltage ranging from 370 to 420mV. The microbial community within the reactor comprised diverse electricity-producing bacteria and AnAOB. This study highlights the excellent denitrification and power generation potential of Anammox AFB-MFC under low energy consumption conditions and provides theoretical groundwork for the practical implementation of Anammox.

Optimizing Continuous Flow Biocatalysis with 3D‐Printing and Inline IR Monitoring

Enzymatic biocatalysis typically generates less waste, uses less water, and minimizes energy consumption compared to traditional chemical methods. Efficient, cell‐free biosynthesis relies on the reuse of its valuable biocatalysts. Immobilization of enzymes on solid supports, such as enzyme carrier resins (ECRs), offers a reliable and widely deployed approach to maximize enzyme turnover in cell‐free biosynthesis. We focus on two major bottlenecks associated with optimizing cell‐free biocatalysis. First, we apply our lab’s 3D‐printed labware to screen ECRs in 96‐well mini‐reactors to optimize enzyme immobilization conditions. Second, we introduce inline infrared spectroscopy to monitor bioreactor output and maximize enzyme productivity. Urease provides a model system for examining immobilization conditions and continuous assessment of biocatalyst performance. As required for the high substrate concentrations to improve process efficiency and minimize waste, urease was studied in unusually high concentrations of its substrate—molar concentrations of urea. The optimized reactor processed 3.24 L of 4.00 M urea at an average volumetric productivity of 13 g·L‐1·h‐1 over 18 h and achieved an estimated productivity number of >17.4 kg urea processed per g of immobilized urease Type‐IX. This workflow can be generalized to most biocatalytic processes and could accelerate adoption of cell‐free biosynthesis for greater chemical sustainability.

In silico simulation of glycosylation and related pathways.

Glycans participate in a vast number of recognition systems in diverse organisms in health and in disease. However, glycans cannot be sequenced because there is no sequencer technology that can fully characterize them. There is no "template" for replicating glycans as there are for amino acids and nucleic acids. Instead, glycans are synthesized by a complicated orchestration of multitudes of glycosyltransferases and glycosidases. Thus glycans can vary greatly in structure, but they are not genetically reproducible and are usually isolated in minute amounts. To characterize (sequence) the glycome (defined as the glycans in a particular organism, tissue, cell, or protein), glycosylation pathway prediction using in silico methods based on glycogene expression data, and glycosylation simulations have been attempted. Since many of the mammalian glycogenes have been identified and cloned, it has become possible to predict the glycan biosynthesis pathway in these systems. By then incorporating systems biology and bioprocessing technologies to these pathway models, given the right enzymatic parameters including enzyme and substrate concentrations and kinetic reaction parameters, it is possible to predict the potentially synthesized glycans in the pathway. This review presents information on the data resources that are currently available to enable in silico simulations of glycosylation and related pathways. Then some of the software tools that have been developed in the past to simulate and analyze glycosylation pathways will be described, followed by a summary and vision for the future developments and research directions in this area.

In silico model development and optimization of in vitro lung cell population growth.

Tissue engineering predominantly relies on trial and error in vitro and ex vivo experiments to develop protocols and bioreactors to generate functional tissues. As an alternative, in silico methods have the potential to significantly reduce the timelines and costs of experimental programs for tissue engineering. In this paper, we propose a methodology to formulate, select, calibrate, and test mathematical models to predict cell population growth as a function of the biochemical environment and to design optimal experimental protocols for model inference of in silico model parameters. We systematically combine methods from the experimental design, mathematical statistics, and optimization literature to develop unique and explainable mathematical models for cell population dynamics. The proposed methodology is applied to the development of this first published model for a population of the airway-relevant bronchio-alveolar epithelial (BEAS-2B) cell line as a function of the concentration of metabolic-related biochemical substrates. The resulting model is a system of ordinary differential equations that predict the temporal dynamics of BEAS-2B cell populations as a function of the initial seeded cell population and the glucose, oxygen, and lactate concentrations in the growth media, using seven parameters rigorously inferred from optimally designed in vitro experiments.

Bimolecular optimization of cellulase production by <i>Richoderma citrinoviride</i> and <i>Aspergillus niger</i> isolates on corn cob, rice bran and sorghum bran as biomass substrates

This work focuses on the assessment of the conditions relevant for the improvement of enzymes hydrolysis of pretreated corn cob, rice bran and sorghum bran by using Trichoderma Citrinoviride and Aspergillus niger. To achieve this, different fermentation conditions were applied to assess their effect in the optimization of cellulase production. Effects of fermentation duration, inoculation size, temperature and pH of fermentation on cellulase production were investigated. At 96 hrs of fermentation, maxim cellusale product was found to be at optimum in both organisms. Hence, 6% substrates concentration with 10 discs of 8mm inoculum size yielded maximum cellulase production in both A. niger and T. citrinoviride after 5 days of incubation. At 35ºC, A niger and T citrinoviride recorded maximum cellulase production 0.50 mg/ml in sorghum bran while 40ºC was optimum for maximum cellulase production for T, citrinoviride on corn cob. Whereas, pH 5.0 T. citrinoviride exhibits maximum cellulase production with sorghum bran 1.30 mg/ml compared to carboxymetyyl cellulose which served as control and sorghum bran 1.2mg/ml. These results highlight the potentials of T. citrinoviride as species of fungus for the industrial production of cellulase using Agricultural wastes as substrates. Cellulase yield was repressed in the presence of glucose and was induced in the presence of corn cob, rice bran and sorghum using T. citrinoviride. Cellulase yield from Corn cob, rice bran and sorghum bran differed significantly at (P<0.05) from glucose.

Facile Asymmetric Syntheses of Non-Natural Amino Acid (S)-Cyclopropylglycine by the Developed NADH-Driven Biocatalytic System

A self-sufficient bifunctional enzyme integrating reductive amination and coenzyme regeneration activities was developed and successfully employed to synthesize (S)-cyclopropylglycine with an improved reaction rate 2.1-fold over the native enzymes and a short bioconversion period of 6 h at a high substrate concentration of 120 g·L−1 and space–time yield of (S)-cyclopropylglycine up to 377.3 g·L−1·d−1, higher than that of any previously reported data. Additionally, (S)-cyclopropylglycine could be continuously synthesized for 90 h with the enzymes packed in a dialysis tube, providing 634.6 g of (S)-cyclopropylglycine with >99.5% ee and over 95% conversion yield up to 12 changes. These results confirmed that the newly developed NADH-driven biocatalytic system could be utilized as a self-sufficient biocatalyst for industrial application in the synthesis of (S)-cyclopropylglycine, which provides a chiral center and cyclopropyl fragment for the frequent synthesis of preclinical/clinical drug molecules.

Unlocking potential: Exploring the methane production potential in anaerobic co-digestion of cassava wastewater and glycerol

This study aimed at evaluating the feasibility of CH4 production in a mesophilic (30 °C) single-stage anaerobic co-digestion of cassava wastewater (CW) and glycerol in an anaerobic fluidized bed reactor (AFBR) with mixing ratio of 50 % / 50 % CW/Gly on a (chemical oxygen demand)COD basis. Thus, the following strategy was used: increasing the organic loading rate (OLR) (1–20 g COD.L−1.d−1) by increasing the substrate concentration (1–20 g COD.L−1) and applying a hydraulic detention time (HRT) of 24 h. The AFBR presented a maximum methane (CH4) content of 88.38±1.94 % and a CH4 yield (MY) of 293.48±18.37 mL of CH4.mL−1CODrem in the OLR of 1 g COD.L−1.d−1 and the maximum methane production rate (MPR) of 62.09±2.75 mL of CH4.L−1.h−1 in the OLR of 20 g COD.L−1.d−1. The conversion of glycerol and carbohydrates remained above 91±0.54 % and 82±2.79 %, respectively, and the COD conversion was above 80±0.65 %. The main metabolites were HAc, HPr, HBu, EtOH and HVa. The most abundant genera identified in the AFBR were Izemoplasmatales and Enterobacteriaceae for the bacteria domain, and Methanosaeta, Methanobacterium for the archaea domain. The single-stage system is robust and can operate with higher OLR without reducing the efficiency of wastewater treatment and CH4 production.

Local Self-Assembly of Dissipative Structures Sustained by Substrate Diffusion.

The coupling between energy-consuming molecular processes and the macroscopic dimension plays an important role in nature and in the development of active matter. Here, we study the temporal evolution of a macroscopic system upon the local activation of a dissipative self-assembly process. Injection of surfactant molecules in a substrate-containing hydrogel results in the local substrate-templated formation of assemblies, which are catalysts for the conversion of substrate into waste. We show that the system develops into a macroscopic (pseudo-)non-equilibrium steady state (NESS) characterized by the local presence of energy-dissipating assemblies and persistent substrate and waste concentration gradients. For elevated substrate concentrations, this state can be maintained for more than 4 days. The studies reveal an interdependence between the dissipative assemblies and the concentration gradients: catalytic activity by the assemblies results in sustained concentration gradients and, vice versa, continuous diffusion of substrate to the assemblies stabilizes their size. The possibility to activate dissipative processes with spatial control and create long lasting non-equilibrium steady states enables dissipative structures to be studied in the space-time domain, which is of relevance for understanding biological systems and for the development of active matter.

Local Self‐Assembly of Dissipative Structures Sustained by Substrate Diffusion

The coupling between energy‐consuming molecular processes and the macroscopic dimension plays an important role in nature and in the development of active matter. Here, we study the temporal evolution of a macroscopic system upon the local activation of a dissipative self‐assembly process. Injection of surfactant molecules in a substrate‐containing hydrogel results in the local substrate‐templated formation of assemblies, which are catalysts for the conversion of substrate into waste. We show that the system develops into a macroscopic (pseudo‐)non‐equilibrium steady state (NESS) characterized by the local presence of energy‐dissipating assemblies and persistent substrate and waste concentration gradients. For elevated substrate concentrations, this state can be maintained for more than 4 days. The studies reveal an interdependence between the dissipative assemblies and the concentration gradients: catalytic activity by the assemblies results in sustained concentration gradients and, vice versa, continuous diffusion of substrate to the assemblies stabilizes their size. The possibility to activate dissipative processes with spatial control and create long lasting non‐equilibrium steady states enables dissipative structures to be studied in the space‐time domain, which is of relevance for understanding biological systems and for the development of active matter.

Metabolic Tug-of-War between Glycolysis and Translation Revealed by Biochemical Reconstitution.

Inside cells, various biological systems work cooperatively for homeostasis and self-replication. These systems do not work independently as they compete for shared elements like ATP and NADH. However, it has been believed that such competition is not a problem in codependent biological systems such as the energy-supplying glycolysis and the energy-consuming translation system. In this study, we biochemically reconstituted the coupling system of glycolysis and translation using purified elements and found that the competition for ATP between glycolysis and protein synthesis interferes with their coupling. Both experiments and simulations revealed that this interference is derived from a metabolic tug-of-war between glycolysis and translation based on their reaction rates, which changes the threshold of the initial substrate concentration for the success coupling. By the metabolic tug-of-war, translation energized by strong glycolysis is facilitated by an exogenous ATPase, which normally inhibits translation. These findings provide chemical insights into the mechanism of competition among biological systems in living cells and provide a framework for the construction of synthetic metabolism in vitro.

Immobilization of an endophytic Bacillus sp. on Phragmites karka stem for lipase production in the presence of Cassia fistula seeds

AbstractEndophytic bacteria have not been reported widely for their lipolytic abilities, so they are not used for large‐scale lipase production. The purpose of this study was to explore an endophytic bacterium for the production of lipase implementing cost‐effective techniques, including the use of Cassia fistula seeds, as a substrate in the production medium and stem pieces of Phragmites karka as the immobilization matrix. The endophytic strain Bacillus sp. E4 was originally isolated from the halophytic plant Arthrocnemum macrostachyum. Bacillus sp. E4 produced 6.05 IU mL−1 lipase in the presence of powdered seeds of Cassia fistula (golden shower tree). Initial trial experiments using a one‐factor‐at‐a‐time approach led to an improvement in lipase titers to 10.05 IU mL−1. Consequently, investigations using the Plackett–Burman design suggested the influence of three significant factors – incubation period, inoculum size, and substrate concentration – on lipase production. They were optimized using the Box–Behnken design (BBD). In the response optimization experiment, strain E4 yielded 52.35 IU mL−1 lipase, which was in accordance with the predicted yield and indicated an overall 8.65 fold improvement in lipase production. To investigate the use of free cells, strain E4 was immobilized on the stem pieces of a halophytic plant, Phragmites karka, which was used for the first time as an immobilization matrix. The immobilized cells retained lipase production ability for up to six cycles with the highest yield of 110 IU mL−1, which corresponded to an improvement of more than eighteenfold. Scanning electron micrographs confirmed the colonization of E4 cells in the matrix and demonstrated the utilization of C. fistula seeds. Fourier transform infrared spectroscopy affirmed the utilization of components including fatty acids by the immobilized E4 cells. The study suggests that endophytic bacterial strains could be applied for the production of lipase with the utilization of nontraditional oil sources.

Identification and structure-based engineering of a dipeptidase CpPepD from Clostridium perfringens for the synthesis of l-carnosine

l-Carnosine (l-Car), an endogenous dipeptide presents in muscle and brain tissues of various vertebrates, has a wide range of application values. The enzymatic preparation of l-Car is a promising synthetic method because it avoids the protection and deprotection steps. In the present study, a dipeptidase gene (CpPepD) from Clostridium perfringens with high l-Car synthetic activity was cloned and characterized. In an effort to improve the performance of this enzyme, we carried out site saturation mutagenesis using CpPepD as the template. By the o-phthalaldehyde (OPA)-derived high throughput screening method, mutant A171S was obtained with 2.2-fold enhanced synthetic activity. The enzymatic properties of CpPepD and mutant A171S were investigated. Under the optimized conditions, 63.94 mM (14.46 g L−1) or 67.02 mM (15.16 g L−1) l-Car was produced at the substrate concentrations of 6 M β-Ala and 0.2 M l-His using wild-type or mutant A171S enzyme, respectively. Although the mutation enhanced the enzyme activity, the reaction equilibrium was barely affected.

The Michaelis–Menten Reaction at Low Substrate Concentrations: Pseudo-First-Order Kinetics and Conditions for Timescale Separation

We demonstrate that the Michaelis–Menten reaction mechanism can be accurately approximated by a linear system when the initial substrate concentration is low. This leads to pseudo-first-order kinetics, simplifying mathematical calculations and experimental analysis. Our proof utilizes a monotonicity property of the system and Kamke’s comparison theorem. This linear approximation yields a closed-form solution, enabling accurate modeling and estimation of reaction rate constants even without timescale separation. Building on prior work, we establish that the sufficient condition for the validity of this approximation is s0≪K\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$s_0 \\ll K$$\\end{document}, where K=k2/k1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K=k_2/k_1$$\\end{document} is the Van Slyke–Cullen constant. This condition is independent of the initial enzyme concentration. Further, we investigate timescale separation within the linear system, identifying necessary and sufficient conditions and deriving the corresponding reduced one-dimensional equations.

Fructooligosaccharides: Production by recombinant fructosyltransferase from Festuca arundinacea in a continuous reactor and kinetic modeling profile

In the quest for maximum conversion of sucrose into 1-kestose using fructosyltransferases in a continuous reactor, consideration of the reversible reactions at competing concentrations of sucrose and 1-kestose is crucial. In this study, a kinetic model based on a combined approach of rapid equilibrium and steady-state kinetics was developed to predict the profile of FOS production using recombinant sucrose: sucrose 1-fructosyltransferase from Festuca arundinacea produced in Pichia pastoris. The purified enzyme selectively converted sucrose into 1-kestose with a final yield of 0.66 g/g sucrose consumed. The reaction rate laws adequately described the kinetic profile of the substrate and the products and accurately predicted the composition of the reaction mixture. The model was fitted to experimental data obtained at three enzyme dosages and three initial sucrose concentrations. The model could predict the effect of substrate concentration on initial rate kinetics, half-saturation constant, and transferase to hydrolase ratio. For the known values of initial sucrose and enzyme concentration, the optimum reaction time and the required dilution rate were predicted for the development of a continuous process to produce 1-kestose-enriched short-chain FOS. A volumetric productivity of ∼110 g/L/h of 1-kestose with 40% carbohydrate composition in the permeate flux was demonstrated.

Kinetic study of photoreactions in an automatic single-liquid-slug oscillatory flow platform

Herein, an automatic single-liquid-slug oscillatory flow platform was established for the kinetic investigation of photochemical reactions. Reaction parameters including concentration, reaction time, light intensity, pressure, and temperature were controlled precisely in an automatic manner, and the reaction outcomes were obtained accurately via, integration of an online HPLC. With the reaction kinetics measurement performed for the photocatalytic oxidation of citronellol by Ru(bpy)3Cl2 at a volume scale of 50 μL, it was demonstrated that the single-liquid-slug oscillatory flow method was capable of achieving material and time savings of 70 % and 38 % respectively as compared to the conventional batch method, and of 80 % and 62 % respectively as compared to the continuous flow method. The four reaction orders manifesting the effects of the substrate concentration, photocatalyst concentration, light intensity, and oxygen pressure, respectively, were attained as well as the photoreaction rate constant. Furthermore, the kinetic data obtained under a series of temperatures also shed light on the photoreaction mechanism which exhibited a relationship between the photoreaction rate constant and temperature that deviated from the Arrhenius law. The approach developed in this work is especially useful for the kinetic studies of photoreactions with relatively slower intrinsic reaction kinetics, achieving a more resource-efficient practice with higher repeatability and accuracy.

Nonlinear Reaction-Diffusion and Mediated Electron Transfer Process at Conducting Polymer Modified Ultramicroelectrodes

The primary goal of this article is to present novel analytical solutions for the coupled nonlinear equation found in the mediated electron transfer process at polymer-modified conducting ultramicroelectrodes. Taylor’s series method is utilized to obtain approximate analytical solutions for the reaction-diffusion equations, allowing for the determination of the substrate and mediator concentrations and the current response concerning the substrate concentration at the electrode’s surface. The impact of different factors on concentration and current is also explored. The derived analytical results are in strong agreement with numerical results and with other analytical outcomes from the literature.

Environmental and genetic influence on the rate and spectrum of spontaneous mutations in Escherichia coli.

Spontaneous mutations are the ultimate source of novel genetic variation on which evolution operates. Although mutation rate is often discussed as a single parameter in evolution, it comprises multiple distinct types of changes at the level of DNA. Moreover, the rates of these distinct changes can be independently influenced by genomic background and environmental conditions. Using fluctuation tests, we characterized the spectrum of spontaneous mutations in Escherichia coli grown in low and high glucose environments. These conditions are known to affect the rate of spontaneous mutation in wild-type MG1655, but not in a ΔluxS deletant strain - a gene with roles in both quorum sensing and the recycling of methylation products used in E. coli's DNA repair process. We find an increase in AT>GC transitions in the low glucose environment, suggesting that processes relating to the production or repair of this mutation could drive the response of overall mutation rate to glucose concentration. Interestingly, this increase in AT>GC transitions is maintained by the glucose non-responsive ΔluxS deletant. Instead, an elevated rate of GC>TA transversions, more common in a high glucose environment, leads to a net non-responsiveness of overall mutation rate for this strain. Our results show how relatively subtle changes, such as the concentration of a carbon substrate or loss of a regulatory gene, can substantially influence the amount and nature of genetic variation available to selection.

Biotechnological Biosuccinic acid (Bio-SA) production from green microalgae Chlorella sp. hydrolysate: Synergistic effect of agitation and substrate concentration assessment using RSM

This paper evaluates the potential of Chlorella sp. microalgae biomass as a feedstock for biosuccinic acid (bio-SA) production via the fermentation process. In this study, the biomass was pretreated and hydrolyzed using a mild acid before being fermented with Actinobacillus succinogenes. The influence of the initial biomass concentration and agitation rate on bio-SA production during batch fermentation was evaluated using a Response Surface Methodology (RSM) design. The results of the study indicated that Chlorella sp. microalgae biomass contained various types of sugars, with glucose identified as the dominant reducing sugar in the Chlorella sp. hydrolysate. According to the RSM analysis, the study showed that changes in the initial biomass concentration and agitation rate could significantly affect bio-SA production from Chlorella sp. hydrolysate. The highest bio-SA concentration of 14.56 g/L with a yield of 0.62 g/g was achieved when fermentation was performed using 10% (w/v) biomass at 150 rpm. Therefore, this study suggests that Chlorella sp. hydrolysate can be an alternative and renewable feedstock for efficient bio-SA production.

Kinetics-based inference of environment-dependent microbial interactions and their dynamic variation.

Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. The effectiveness of our method was experimentally demonstrated using a synthetic consortium of two Escherichia coli mutants that are metabolically dependent (due to an inability to synthesize essential amino acids) but competitively grow on a shared substrate. The analysis of the E. coli binary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions, such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer the complex dynamics of microbial communities. Moreover, the prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among macroorganisms, such as plants and animals, as well as microorganisms.

Solvent-promoted selective chemocatalytic hydroxymethylation of biomass furanic compounds

Functionalizing biomass-derived furanic chemicals is of great importance towards biorefinery processes but challenging, especially working at elevated substrate concentrations. We herein report the intervention of 1,4-dioxane co-solvent availably to catalyze hydroxymethylation of furfuryl alcohol (FA) in formalin over Hβ zeolite, giving high yield to 2,5-dihydroxymethylfuran (DHMF), a versatile building block. Impressively, the facilitating effect of 1,4-dioxane on DHMF production became more pronounced with increasing FA feeding concentration, and the yield raised from 19.5 % to 67.8 % from a high FA concentration of 10 wt%. The 1,4-dioxane served not only as a catcher of formaldehyde hydrate to access substrate FA, but also as a shield to restrain undesirable condensation side-reactions. The developed protocol demonstrated an excellent universality in boosting the hydroxymethylation of electrondrawing-group-free furanic molecules (e.g., furan, 2-methylfuran). The understanding of these solvation effects can be employed to effectively manipulate and improve the hydroxymethylation of furanic compounds.