Molecular and Engineering Perspectives of the Biocatalysis Interface to Chemical Synthesis

The sustainable use of limited resources by nature to provide target molecules with biocatalytic reactions continues to be a role model for chemical synthesis. The application of biocatalysts to functional group transformations is shaped by the various parallel influences like e.g. the search for selectivity, the shift from fossil-based to biobased raw materials and the economy of molecular transformations like atom economy and step economy. As safety, health and environment issues are key drivers for process improvements in the chemical industry, the development of reactions or pathways replacing hazardous reagents is another major factor determining the sequence of molecular transformations from raw material to product. Biocatalyst production technologies and integrated process engineering have been instrumental in the establishment of biocatalytic reaction steps in chemical synthesis. The inherent properties of biocatalysts make them the privileged catalysts for highly selective asymmetric molecular transformations like e.g. hydrolysis reactions, oxidation reactions, carbon-carbon bond formation reactions as well as molecular unit transfer reactions. The universe of six enzyme classes provides a tremendous goldmine for discovering improved versions of enzymes with known functions as well as for finding completely novel enzymes. With the growing collection of biocatalytic reactions, the retrosynthetic thinking from chemical synthesis can be applied to biocatalysis as well. Once the feasibility of a biocatalytic reaction has been proven, up- and downscaling experiments have been useful for engineering the most adequate process design. In the case of the first large-scale biocatalytic Baeyer-Villiger oxidation, the debottlenecking of the substrate feed and product recovery, final purification and overcoming thermodynamic limitations have been essential in establishing bioprocesses with high yields of enantiopure products. These downscaling experiments in conjunction with new analytical techniques have proven useful also in the case of asymmetric synthesis of natural compounds. Spatial and temporal organisation of biocatalysts, reactants or products is another interesting engineering option for biocatalytic process design. The interdisciplinary character of the dead ends and locks between chemistry, biology and engineering requires investigations of the interfaces. Communication across scientific and technological disciplines including the value creation perspective is important for the development of a better synthesis for the final product-in-the-bottle. Whether the successful problem solution will come from the engineering of substrates, reaction media, process conditions or from the search for better and new enzymes, progress in the understanding of the molecular mechanisms of enzyme action will be key for the further development of the science of synthesis with its challenges towards the more difficult and more complex target molecules

Biocatalytic Process Design and Reaction Engineering

Biocatalytic processes occurring in nature provide a wealth of inspiration for manufacturing processes with high molecular economy. The molecular and engineering aspects of bioprocesses converting available raw materials into valuable products are therefore of much industrial interest. Modular reaction platforms and straightforward working paths, from the fundamental understanding of biocatalytic systems in nature to the design and reaction engineering of novel biocatalytic processes, have been important for shortening development times. Building on broadly applicable reaction platforms and tools for designing biocatalytic processes and their reaction engineering are key success factors. Process integration and intensification aspects are illustrated with biocatalytic processes to numerous small-molecular weight compounds, which have been prepared by novel and highly selective routes, for applications in the life sciences and biomedical sciences. This work is licensed under a Creative Commons Attribution 4.0 International License

A one-pot hydrothermal synthesis of sulfur and nitrogen doped carbon aerogels with enhanced electrocatalytic activity in the oxygen reduction reaction

A one-pot, hydrothermal synthesis of nitrogen and sulfur dual doped carbon aerogels is presented, derived from our previously published hydrothermal carbonization approach. Two co-monomers, S-(2-thienyl)-L-cysteine (TC) and 2-thienyl carboxaldehyde (TCA), were used for sulfur incorporation, giving rise to distinct morphologies and varying doping levels of sulfur. Nitrogen-doping levels of 5 wt% and sulfur-doping levels of 1 wt% (using TCA) to 4 wt% (using TC) were obtained. A secondary pyrolysis step was used to further tune the carbon aerogel conductivity and heteroatom binding states. By comparing solely nitrogen-doped with nitrogen- and sulfur-doped carbon aerogels, it was observed that the presence of sulfur improves the overall electrocatalytic activity of the carbon material in both basic and acidic media. This study of the synergistic effect of combined sulfur- and nitrogen-doping in the catalysis of the “oxygen reduction reaction” (ORR) is expected to be significant to future research concerning the improvement of heterogeneous, metal-free, carbon-based catalysts

Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis

This is the final version. Available on open access from Frontiers Media via the DOI in this recordThe biosynthesis of metabolites from available starting materials is becoming an ever important area due to the increasing demands within the life science research area. Access to metabolites is making essential contributions to analytical, diagnostic, therapeutic and different industrial applications. These molecules can be synthesized by the enzymes of biological systems under sustainable process conditions. The facile synthetic access to the metabolite and metabolite-like molecular space is of fundamental importance. The increasing knowledge within molecular biology, enzyme discovery and production together with their biochemical and structural properties offers excellent opportunities for using modular cell-free biocatalytic systems. This reduces the complexity of synthesizing metabolites using biological whole-cell approaches or by classical chemical synthesis. A systems biocatalysis approach can provide a wealth of optimized enzymes for the biosynthesis of already identified and new metabolite molecules

Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry.

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection

Conscious coupling: The challenges and opportunities of cascading enzymatic microreactors

The continuous production of high value or difficult to synthesize products is of increasing interest to the pharmaceutical industry. Cascading reaction systems have already been employed for chemical synthesis with great success, allowing a quick change in reaction conditions and addition of new reactants as well as removal of side products. A cascading system can remove the need for isolating unstable intermediates, increasing the yield of a synthetic pathway. Based on the success for chemical synthesis, the question arises how cascading systems could be beneficial to chemo-enzymatic or biocatalytic synthesis. Microreactors, with their rapid mass and heat transfer, small reaction volumes and short diffusion pathways, are promising tools for the development of such processes. In this mini-review, the authors provide an overview of recent examples of cascaded microreactors. Special attention will be paid to how microreactors are combined and the challenges as well as opportunities that arise from such combinations. Selected chemical reaction cascades will be used to illustrate this concept, before the discussion is widened to include chemo-enzymatic and multi-enzyme cascades. The authors also present the state of the art of online and at-line monitoring for enzymatic microreactor cascades. Finally, the authors review work-up and purification steps and their integration with microreactor cascades, highlighting the potential and the challenges of integrated cascades

Do You Know What You Owe? Students\u27 Understanding of Their Student Loans

Using a data set that augments a student survey with administrative data from the Iowa State University Office of Financial Aid, the authors posed two questions: Do students know whether they have student loans? Do students know how much they owe on outstanding student loans? We used logistic and ordered logit regressions to answer these questions. Results suggest that although the majority of students are aware that they owe on student loans, many underestimate the amount they owe. One eighth of students in the current study reported no student debt when, in fact, they had a loan. Over a quarter of the students underestimated the amount they owed by less than $10,000, and nearly one tenth of students underestimated the amount that they owed by more than$10,000. This article discusses the roles that counselors, educators, and policy makers can play in improving students’ understanding of their student loan debt

Slower growth prior to the 2018 drought and a high growth sensitivity to previous year summer conditions predisposed European beech to crown dieback.

The record-breaking drought in 2018 caused premature leaf discoloration and shedding (early browning) in many beech (Fagus sylvatica L.) dominated forests in Central Europe. However, a high degree of variability in drought response among individual beech trees was observed. While some trees were severely impacted by the prolonged water deficits and high temperatures, others remained vital with no or only minor signs of crown vitality loss. Why some beech trees were more susceptible to drought-induced crown damage than others and whether growth recovery is possible are poorly understood. Here, we aimed to identify growth characteristics associated with the variability in drought response between individual beech trees based on a sample of 470 trees in northern Switzerland. By combining tree growth measurements and crown condition assessments, we also investigated the possible link between crown dieback and growth recovery after drought. Beech trees with early browning exhibited an overall lower growth vigor before the 2018 drought than co-occurring vital beech trees. This lower vigor is mainly indicated by lower overall growth rates, stronger growth declines in the past decades, and higher growth-climate sensitivity. Particularly, warm previous year summer conditions negatively affected current growth of the early-browning trees. These findings suggest that the affected trees had less access to critical resources and were physiologically limited in their growth predisposing them to early browning. Following the 2018 drought, observed growth recovery potential corresponded to the amount of crown dieback and the local climatic water balance. Overall, our findings emphasize that beech-dominated forests in Central Europe are under increasing pressure from severe droughts, ultimately reducing the competitive ability of this species, especially on lowland sites with shallow soils and low water holding capacity