Oxidative Coupling of Methane: A Review Study on the Catalytic Performance.

Extensive data on the characteristics and performance of the catalysts synthesized and tested for methane oxidative coupling (OCM) is available in thousands of reports published during the last four decades. Revisiting and analyzing the general trends recognizable in those data could improve the current understanding of the catalyst functionality under different reaction conditions. This is instrumental in determining the direction of future research aiming for more efficient OCM catalysts and reactors. These are the subjects of the comprehensive analysis reported in this paper, which covers the main aspects associated with the analysis of the OCM catalytic performance, including the catalyst characteristics, reaction mechanism, and reactor operation. Special attention was devoted to analyzing these aspects in the framework of thermal-reaction engineering and, accordingly, critically reviewing the reported catalytic performances in the literature.

[Application prospect of reaction engineering approach in studying drying behavior of single droplet during spray drying of traditional Chinese medicine].

Spray drying technology is one of the most commonly used unit operations in the production of traditional Chinese medicine(TCM) preparations, offering advantages such as short drying time and uniform product quality. However, due to the properties of TCM extracts, such as high viscosity, strong hygroscopicity, and poor flowability, there is limited scope to solve the problems of wall adhesion and clumping in spray drying from the macroscopic perspective of pharmaceutical production. Therefore, it has become a trend to study and optimize the spray drying process from the microscopic point of view by investigating single droplet evaporation behavior. Based on the reaction engineering approach(REA), the single droplet drying system, as a novel method for studying droplets, collects parameter data on individual TCM droplets during the drying process and uses the REA to process the data and establish predictive models. This approach is crucial for understanding the mechanism of TCM spray drying. This paper summarized and analyzed the cha-racteristics of various single droplet systems, the application of REA in single droplet drying systems, and its significance in optimizing the process, predicting drying states, and shortening the development cycle in the field of TCM spray drying, and looked ahead to the prospects of this method, including the introduction of new parameters and imaging techniques, aiming to provide a reference for further research in the field of TCM spray drying.

Rational orthologous pathway and biochemical process engineering for adipic acid production using Pseudomonas taiwanensis VLB120.

Microbial bioprocessing based on orthologous pathways constitutes a promising approach to replace traditional greenhouse gas- and energy-intensive production processes, e.g., for adipic acid (AA). We report the construction of a Pseudomonas taiwanensis strain able to efficiently convert cyclohexane to AA. For this purpose, a recently developed 6-hydroxyhexanoic acid (6HA) synthesis pathway was amended with alcohol and aldehyde dehydrogenases, for which different expression systems were tested. Thereby, genes originating from Acidovorax sp. CHX100 and the XylS/Pm regulatory system proved most efficient for the conversion of 6HA to AA as well as the overall cascade enabling an AA formation activity of up to 48.6 ± 0.2 U gCDW-1. The optimization of biotransformation conditions enabled 96% conversion of 10 mM cyclohexane with 100% AA yield. During recombinant gene expression, the avoidance of glucose limitation was found to be crucial to enable stable AA formation. The biotransformation was then scaled from shaking flask to a 1 L bioreactor scale, at which a maximal activity of 22.6 ± 0.2 U gCDW-1 and an AA titer of 10.2 g L-1 were achieved. The principal feasibility of product isolation was shown by the purification of 3.4 g AA to a purity of 96.1%. This study presents the efficient bioconversion of cyclohexane to AA by means of a single strain and thereby sets the basis for an environmentally benign production of AA and related polymers such as nylon 6,6.

Selectivity and kinetic modeling of penicillin G acylase variants for the synthesis of cephalexin under a broad range of substrate concentrations.

The kinetics of cephalexin synthesis and hydrolysis of the activated acyl-donor precursor phenylglycine methyl ester (PGME) were characterized under a broad range of substrate concentrations. A previously developed model by Youshko-Svedas involving the formation of the acyl-enzyme complex followed by binding of the nucleophilic ß-lactam donor does not fully estimate the maximum reaction yields for cephalexin synthesis at different concentrations using initial-rate data. 7-aminodesacetoxycephalosporanic acid (7-ADCA) was discovered to be a potent inhibitor of cephalexin hydrolysis, which may account for the deviation from model predictions. Three kinetic models were compared for cephalexin synthesis, with the model incorporating competitive inhibition due to 7-ADCA yielding the best fit. Additionally, the ßF24A variant and Assemblase® did not exhibit significantly different kinetics for the synthesis of cephalexin compared to the wild-type, for the concentration range evaluated and for both initial-rate experiments and time-course synthesis experiments. Lastly, a continuous stirred-tank reactor for cephalexin synthesis was simulated using the model incorporating competitive inhibition by 7-ADCA, with clear tradeoffs observed between productivity, fractional yield, and PGME conversion.

C-H Bond Functionalization under Electrochemical Flow Conditions.

Electrochemical C-H functionalization is a rapidly growing area of interest in organic synthesis. To achieve maximum atom economy, the flow electrolysis process is more sustainable. This allows shorter reaction times, safer working environments, and better selectivities. Using this technology, the problem of overoxidation can be reduced and less emergence of side products or no side products are possible. Flow electro-reactors provide high surface-to-volume ratios and contain electrodes that are closely spaced where the diffusion layers overlap to give the desired product, electrochemical processes can now be managed without the need for a deliberately added supporting electrolyte. Considering the importance of flow electrochemical C-H functionalization, a comprehensive review is presented. Herein, we summarize flow electrolysis for the construction of C-C and C-X (X=O, N, S, and I) bonds formation. Also, benzylic oxidation and access to biologically active molecules are discussed.

A Gram-Scale Limonene Production Process with Engineered Escherichia coli.

Monoterpenes, such as the cyclic terpene limonene, are valuable and important natural products widely used in food, cosmetics, household chemicals, and pharmaceutical applications. The biotechnological production of limonene with microorganisms may complement traditional plant extraction methods. For this purpose, the bioprocess needs to be stable and ought to show high titers and space-time yields. In this study, a limonene production process was developed with metabolically engineered Escherichia coli at the bioreactor scale. Therefore, fed-batch fermentations in minimal medium and in the presence of a non-toxic organic phase were carried out with E. coli BL21 (DE3) pJBEI-6410 harboring the optimized genes for the mevalonate pathway and the limonene synthase from Mentha spicata on a single plasmid. The feasibility of glycerol as the sole carbon source for cell growth and limonene synthesis was examined, and it was applied in an optimized fermentation setup. Titers on a gram-scale of up to 7.3 g·Lorg-1 (corresponding to 3.6 g·L-1 in the aqueous production phase) were achieved with industrially viable space-time yields of 0.15 g·L-1·h-1. These are the highest monoterpene concentrations obtained with a microorganism to date, and these findings provide the basis for the development of an economic and industrially relevant bioprocess.

Convective drying of onion: modeling of drying kinetics parameters.

Drying is a simultaneous heat and mass transfer processes. Drying kinetics is determined by both internal properties and external drying conditions. In this study, two important drying kinetics parameters of onions i.e. effective water diffusivity and relative activation energy of reaction engineering approach (REA) are determined. The generated parameters are used to model thin layer drying of onion at different temperatures (40, 50, 60, and 70 °C) and relative humidity of 20%. The effective water diffusivity is in the range of 2.8 × 10-10 m2 s-1 and 8.1 × 10-10 m2 s-1. Unlike the diffusivity, the relative activation energy of the REA is independent on drying conditions and thus the latter approach requires less effort in generating the transport properties. The transport parameters can be applied for assisting in designing dryer units and evaluating the performance of existing dryer units.

Carbon monoxide conversion with Clostridium aceticum.

Carbon monoxide concentrations in syngas are often high, but tolerance toward CO varies a lot between homoacetogenic bacteria. Analysis of the autotrophic potential revealed that the first isolated acetogenic bacterium Clostridium aceticum was able to use CO as sole carbon and energy source for chemolithoautotrophic carbon fixation but simultaneously showed little tolerance to high CO concentrations. Not yet reported, autotrophic ethanol production by C. aceticum was discovered with CO as a substrate in batch processes. Growth rates estimated in batch processes at varying CO partial pressures were used to identify the CO inhibition kinetics of C. aceticum, using a substrate inhibition model. C. aceticum shows a strong CO inhibition with an optimum CO partial pressure of only 5.4 mbar in the gas phase at cell dry weight concentrations of up to 0.5 g·L -1 . At optimum conditions, growth and acetate formation rates were estimated to be 0.24 hr -1 and 0.52 g·g -1 ·hr -1 , respectively. Syngas fermentation at high partial pressures of up to 280 mbar CO in the inlet gas phase was enabled by applying a continuously operated stirred-tank bioreactor with submerged membranes with total cell retention. Around 70% CO conversion was achieved continuously in the membrane bioreactor with strongly CO inhibited C. aceticum resulting in space-time yields of up to 0.85 g·L -1 ·hr -1 acetate.

Application of a thermostable Baeyer-Villiger monooxygenase for the synthesis of branched polyester precursors.

BACKGROUND: It is widely accepted that the poor thermostability of Baeyer-Villiger monooxygenases limits their use as biocatalysts for applied biocatalysis in industrial applications. The goal of this study was to investigate the biocatalytic oxidation of 3,3,5-trimethylcyclohexanone using a thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) for the synthesis of branched ϵ-caprolactone derivatives as building blocks for tuned polymeric backbones. In this multi-enzymatic reaction, the thermostable cyclohexanone monooxygenase was fused to a phosphite dehydrogenase (PTDH) in order to ensure co-factor regeneration. RESULTS: Using reaction engineering, the reaction rate and product formation of the regio-isomeric branched lactones were improved and the use of co-solvents and the initial substrate load were investigated. Substrate inhibition and poor product solubility were overcome using continuous substrate feeding regimes, as well as a biphasic reaction system with toluene as water-immiscible organic solvent. A maximum volumetric productivity, or space-time-yield, of 1.20 g L-1 h-1 was achieved with continuous feeding of substrate using methanol as co-solvent, while a maximum product concentration of 11.6 g L-1 was achieved with toluene acting as a second phase and substrate reservoir. CONCLUSION: These improvements in key process metrics therefore demonstrate progress towards the up-scaled Baeyer-Villiger monooxygenase-biocatalyzed synthesis of the target building blocks for polymer application. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Kinetic insights into ϵ-caprolactone synthesis: Improvement of an enzymatic cascade reaction.

A computational approach for the simulation and prediction of a linear three-step enzymatic cascade for the synthesis of ϵ-caprolactone (ECL) coupling an alcohol dehydrogenase (ADH), a cyclohexanone monooxygenase (CHMO), and a lipase for the subsequent hydrolysis of ECL to 6-hydroxyhexanoic acid (6-HHA). A kinetic model was developed with an accuracy of prediction for a fed-batch mode of 37% for substrate cyclohexanol (CHL), 90% for ECL, and >99% for the final product 6-HHA. Due to a severe inhibition of the CHMO by CHL, a batch synthesis was shown to be less efficient than a fed-batch approach. In the fed-batch synthesis, full conversion of 100 mM CHL was 28% faster with an analytical yield of 98% compared to 49% in case of the batch synthesis. The lipase-catalyzed hydrolysis of ECL to 6-HHA circumvents the inhibition of the CHMO by ECL enabling a 24% higher product concentration of 6-HHA compared to ECL in case of the fed-batch synthesis without lipase. Biotechnol. Bioeng. 2017;114: 1215-1221. © 2017 Wiley Periodicals, Inc.

Maximization of cell viability rather than biocatalyst activity improves whole-cell ω-oxyfunctionalization performance.

It is a common misconception in whole-cell biocatalysis to refer to an enzyme as the biocatalyst, thereby neglecting the structural and metabolic framework provided by the cell. Here, the low whole-cell biocatalyst stability, that is, the stability of specific biocatalyst activity, in a process for the terminal oxyfunctionalization of renewable fatty acid methyl esters was investigated. This reaction, which is difficult to achieve by chemical means, is catalyzed by Escherichia coli featuring the monooxygenase system AlkBGT and the uptake facilitator AlkL from Pseudomonas putida GPo1. Corresponding products, that is, terminal alcohols, aldehydes, and acids, constitute versatile bifunctional building blocks, which are of special interest for polymer synthesis. It could clearly be shown that extensive dodecanoic acid methyl ester uptake mediated by high AlkL levels leads to whole-cell biocatalyst toxification. Thus, cell viability constitutes the primary factor limiting biocatalyst stability and, as a result, process durability. Hence, a compromise had to be found between low biocatalyst activity due to restricted substrate uptake and poor biocatalyst stability due to AlkL-mediated toxification. This was achieved by the fine-tuning of heterologous alkL expression, which, furthermore, enabled the identification of the alkBGT expression level as another critical factor determining biocatalyst stability. Controlled synthesis of AlkL and reduced alkBGT expression finally enabled an increase of product titers by a factor of 4.3 up to 229 g Lorg-1 in a two-liquid phase bioprocess setup. Clearly, ω-oxyfunctionalization process performance was determined by cell viability and thus biocatalyst stability rather than the maximally achievable specific biocatalyst activity. Biotechnol. Bioeng. 2017;114: 874-884. © 2016 Wiley Periodicals, Inc.

Progress in biocatalysis with immobilized viable whole cells: systems development, reaction engineering and applications.

Viable microbial cells are important biocatalysts in the production of fine chemicals and biofuels, in environmental applications and also in emerging applications such as biosensors or medicine. Their increasing significance is driven mainly by the intensive development of high performance recombinant strains supplying multienzyme cascade reaction pathways, and by advances in preservation of the native state and stability of whole-cell biocatalysts throughout their application. In many cases, the stability and performance of whole-cell biocatalysts can be highly improved by controlled immobilization techniques. This review summarizes the current progress in the development of immobilized whole-cell biocatalysts, the immobilization methods as well as in the bioreaction engineering aspects and economical aspects of their biocatalytic applications.

Decoupling production from growth by magnesium sulfate limitation boosts de novo limonene production.

The microbial production of isoprenoids has recently developed into a prime example for successful bottom-up synthetic biology or top-down systems biology strategies. Respective fermentation processes typically rely on growing recombinant microorganisms. However, the fermentative production of isoprenoids has to compete with cellular maintenance and growth for carbon and energy. Non-growing but metabolically active E. coli cells were evaluated in this study as alternative biocatalyst configurations to reduce energy and carbon loss towards biomass formation. The use of non-growing cells in an optimized fermentation medium resulted in more than fivefold increased specific limonene yields on cell dry weight and glucose, as compared to the traditional growing-cell-approach. Initially, the stability of the resting-cell activity was limited. This instability was overcome via the optimization of the minimal fermentation medium enabling high and stable limonene production rates for up to 8 h and a high specific yield of ≥50 mg limonene per gram cell dry weight. Omitting MgSO4 from the fermentation medium was very promising to prohibit growth and allow high productivities. Applying a MgSO4 -limitation also improved limonene formation by growing cells during non-exponential growth involving a reduced biomass yield on glucose and a fourfold increase in specific limonene yields on biomass as compared to non-limited cultures. The control of microbial growth via the medium composition was identified as a key but yet underrated strategy for efficient isoprenoid production. Biotechnol. Bioeng. 2016;113: 1305-1314. © 2015 Wiley Periodicals, Inc.

Coupling limonene formation and oxyfunctionalization by mixed-culture resting cell fermentation.

Metabolic engineering strategies mark a milestone for the fermentative production of bulk and fine chemicals. Yet, toxic products and volatile reaction intermediates with low solubilities remain challenging. Prominent examples are artificial multistep pathways like the production of perillyl acetate (POHAc) from glucose via limonene. For POHAc, these limitations can be overcome by mixed-culture fermentations. A limonene biosynthesis pathway and cytochrome P450 153A6 (CYP153A6) as regioselective hydroxylase are used in two distinct recombinant E. coli. POHAc formation from glucose in one recombinant cell was hindered by ineffective coupling of limonene synthesis and low rates of oxyfunctionalization. The optimization of P450 gene expression led to the formation of 6.20 ± 0.06 mg gcdw (-1) POHAc in a biphasic batch cultivation with glucose as sole carbon and energy source. Increasing the spatial proximity between limonene synthase and CYP153A6 by a genetic fusion of both enzymes changed the molar limonene/POHAc ratio from 3.2 to 1.6. Spatial separation of limonene biosynthesis from its oxyfunctionalization improved POHAc concentration 3.3-fold to 21.7 mg L(-1) as compared to a biphasic fermentation. Mixed-cultures of E. coli BL21 (DE3) containing the limonene biosynthesis pathway and E. coli MG1655 harboring either CYP153A6, or alternatively a cymene monooxygenase, showed POHAc formation rates of 0.06 or 0.11 U gcdw (-1) , respectively. This concept provides a novel framework for fermentative syntheses involving toxic, volatile, or barely soluble compounds or pathway intermediates.

The yin and yang in the development of catalytic processes: catalysis research and reaction engineering.

For the implementation of commercial catalytic processes, catalyst development and reactor design and engineering need to go hand-in-hand. As both fields are mutually interdependent, a co-evolution of catalysts and chemical reactors has historically been the right path towards successful, large-scale technologies. Over the 150 years of its existence, the contributions of BASF to the development of several commercial catalytic processes constitute perfect illustrations of this necessary and synergetic interplay between catalyst science and reactor engineering.

Reaction engineering strategies for the production of inorganic nanomaterials.

The rapid expansion of nanotechnology requires scaled-up production rates to cope with increased nanomaterials demand. However, in many cases, the final uses of nanomaterials impose strict requisites on their physical and chemical characteristics including size, shape, chemical composition and type of functional groups on their surface. Frequently, additional features such as a limited degree of agglomeration are also demanded. These requisites represent a serious challenge to present-day synthesis methods when nanomaterials must be produced in large amounts. Some of the possible solutions from the reaction engineering perspective are discussed in this work for both gas and liquid phase production processes. Special attention will be devoted to enabling technologies, which allow the production of engineered nanoparticles with limited aggregation and with a good control on their nano-scale characteristics.

[Design and practice of biological reaction engineering flipped classroom in applied undergraduate colleges].

This study aims to explore and refine the teaching aspects of a flipped classroom approach for biological reaction engineering. The study encompasses three iterations of teaching practice, focusing on key elements such as theme content selection, implementation process, evaluation and effectiveness. By integrating relevant industry and societal topics with course's professional knowledge, students are encouraged to independently collect data, analyze and discuss findings, and present their work in group. Comprehensive literacy of students is assessed through discussion reports, defense reports, utilization of new tools, and team cooperation. Analysis of student performance reveals that the design and implementation of the flipped classroom approach significantly enhances student motivation to learn, improves scores, and supports the achievement of course objectives. Therefore, the methodology presented in this study may serve as a reference for implementing teaching reforms in core courses in applied undergraduate colleges, thereby fostering well-round individuals with strong theoretical foundation, innovative analytical skills, and excellent teamwork abilities.

Reaching machine learning leverage to advance performance of electrocatalytic CO2 conversion in non-aqueous deep eutectic electrolytes.

Deep eutectic electrolytes (DEEs) show promise for future electrochemical systems due to their adjustable buffer capacities. This study utilizes machine learning algorithms to analyse the carbon dioxide reduction reaction (CO2RR) in DEEs with a buffer capacity of approximately 10.21 mol/pH. The objective is to minimize undesired hydrogen evolution reactions (HER) and render CO2RR dominant in a membrane cell. The CO2RR process was found to be non-adiabatic, as the time of nuclear motion for CO32- in K2CO3 product, through CO2●- trapping, is 0.368 femtoseconds shorter than the 1.856 × 10-3s charge transfer relaxation time. Microkinetic analysis reveals that the rate of CO2RR to CO2●- is 2.14 × 103 mol/cm2/s2 with a rate constant of 2.1 × 1010 cm/s. Our findings demonstrate that ensemble and k-Nearest Neighbours algorithms learn the CO2RR dataset, achieving a prediction accuracy of over 99%. The models were verified visually and quantitatively by overlaying predicted and experimental dataset. Diagnostic and SHAP analyses highlighted the gradient boost ensemble algorithm, predicting asymptotic current densities of -4.114 mA/cm2 or -13.340 mA/cm2, with high turnover frequencies (TOF) of 3.79 × 1010 h-1 or 12.30 × 1010 h-1 for CO2●- or K2CO3 generation on silver electrodes, respectively. These results consider both accuracy and robustness against overfitting, providing an opportunity to optimize future non-aqueous electrolytes for convenient TOF measurements at industrially relevant current densities.

Carbon nanotubes: an example of multiscale development--a mechanistic view from the subnanometer to the meter scale.

We summarize the catalytic synthesis of multiwall carbon nanotubes (MWCNTs). The current understanding of the reaction mechanism is presented, in particular the catalyst design for the CCVD process is analyzed. To complement that, kinetics and reaction engineering aspects are discussed along with the impact of the reaction and reactor operation on the product properties. All these issues are analyzed from the perspective of the industrial synthesis and implications for the application of carbon nanotubes. Carbon-nanotube technology is a perfect example of multi-scale development and covers challenges from the nanometer to the meter scale. Problems, methods, and solutions characteristic for different scales will be highlighted. The Co/Mn catalyst is used as reference as one of the first commercially used technologies for the scalable production of multiwall carbon nanotubes.

Catalytic atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes via dynamic kinetic resolution.

Reported herein is a highly efficient dynamic kinetic resolution protocol for the atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes. Atropisomers bearing vicinal diaxes mainly exist in o-triaryls, while that of biaryls is highly challenging in terms of the concerted rotation and deplanarization effects. The combination of C-C biaryl with N-N nonbiaryl delivers a novel class of vicinal-diaxis heterobiaryls. For their atroposelective synthesis, the dynamic kinetic resolution enabled by either quinine-catalyzed allylation or isothiourea-catalyzed acylation has been developed, allowing the preparation of a wide range of vicinal-axis heterobiaryls in good yields with excellent enantioselectivities. Atropisomerization experiments revealed that the C-C bond rotation led to diastereomers, and the N-N bond rotation offered enantiomers. Besides, this protocol could be extended to kinetic resolution by employing substrates with a more hindered axis.