To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Microbial Electrosynthesis: Where Do We Go from Here?

The valorization of CO2 to valuable products via microbial electrosynthesis (MES) is a technology transcending the disciplines of microbiology, (electro)chemistry, and engineering, bringing opportunities and challenges. As the field looks to the future, further emphasis is expected to be placed on engineering efficient reactors for biocatalysts, to thrive and overcome factors which may be limiting performance. Meanwhile, ample opportunities exist to take the lessons learned in traditional and adjacent electrochemical fields to shortcut learning curves. As the technology transitions into the next decade, research into robust and adaptable biocatalysts will then be necessary as reactors shape into larger and more efficient configurations, as well as presenting more extreme temperature, salinity, and pressure conditions.</p

Microbial Electrosynthesis: Where Do We Go from Here?

The valorization of CO2 to valuable products via microbial electrosynthesis (MES) is a technology transcending the disciplines of microbiology, (electro)chemistry, and engineering, bringing opportunities and challenges. As the field looks to the future, further emphasis is expected to be placed on engineering efficient reactors for biocatalysts, to thrive and overcome factors which may be limiting performance. Meanwhile, ample opportunities exist to take the lessons learned in traditional and adjacent electrochemical fields to shortcut learning curves. As the technology transitions into the next decade, research into robust and adaptable biocatalysts will then be necessary as reactors shape into larger and more efficient configurations, as well as presenting more extreme temperature, salinity, and pressure conditions.BT/Bioprocess EngineeringChemE/Materials for Energy Conversion & Storag

Editorial: Microbial Electrogenesis, Microbial Electrosynthesis, and Electro-bioremediation

BT/Bioprocess Engineerin

Biomass-specific rates as key performance indicators: A nitrogen balancing method for biofilm-based electrochemical conversion

Microbial electrochemical technologies (METs) employ microorganisms utilizing solid-state electrodes as either electron sink or electron source, such as in microbial electrosynthesis (MES). METs reaction rate is traditionally normalized to the electrode dimensions or to the electrolyte volume, but should also be normalized to biomass amount present in the system at any given time. In biofilm-based systems, a major challenge is to determine the biomass amount in a non-destructive manner, especially in systems operated in continuous mode and using 3D electrodes. We developed a simple method using a nitrogen balance and optical density to determine the amount of microorganisms in biofilm and in suspension at any given time. For four MES reactors converting CO2 to carboxylates, &gt;99% of the biomass was present as biofilm after 69 days of reactor operation. After a lag phase, the biomass-specific growth rate had increased to 0.12–0.16 days−1. After 100 days of operation, growth became insignificant. Biomass-specific production rates of carboxylates varied between 0.08–0.37 molC molX−1d−1. Using biomass-specific rates, one can more effectively assess the performance of MES, identify its limitations, and compare it to other fermentation technologies.</p

A General Model for Biofilm-Driven Microbial Electrosynthesis of Carboxylates From CO₂

Up to now, computational modeling of microbial electrosynthesis (MES) has been underexplored, but is necessary to achieve breakthrough understanding of the process-limiting steps. Here, a general framework for modeling microbial kinetics in a MES reactor is presented. A thermodynamic approach is used to link microbial metabolism to the electrochemical reduction of an intracellular mediator, allowing to predict cellular growth and current consumption. The model accounts for CO2 reduction to acetate, and further elongation to n-butyrate and n-caproate. Simulation results were compared with experimental data obtained from different sources and proved the model is able to successfully describe microbial kinetics (growth, chain elongation, and product inhibition) and reactor performance (current density, organics titer). The capacity of the model to simulate different system configurations is also shown. Model results suggest CO2 dissolved concentration might be limiting existing MES systems, and highlight the importance of the delivery method utilized to supply it. Simulation results also indicate that for biofilm-driven reactors, continuous mode significantly enhances microbial growth and might allow denser biofilms to be formed and higher current densities to be achieved.BT/Bioprocess Engineerin

Designer Discodermolide Segments via Ozonolysis of Vinyl Phosphonates

To apply our collection of enantiopure 7-ring vinyl sulfones to probe the anticancer SAR of a series of computer-designed (+)-discodermolide analogs, the ozonolytic reactivity of transposed cyclic vinyl phosphonates was explored. Successful preparation of the desired aldehyde-esters and lactones from vinyl phosphonates via an oxidative cleavage−phosphite/methanol exchange sequence is described

Asymmetric Synthesis of All Eight Seven-Carbon Dipropionate Stereotetrads

Enantiopure cycloheptadienyl sulfones 6 and 7 are diastereoselectively epoxidized to yield epoxyvinyl sulfones 8, 9, 14, and 16 in high yields and diastereomeric ratios. Syn and anti methylation of epoxides 8, 9, 14, and 16 enables access to all eight possible diastereomeric stereotetrads, seven of which are commonly found in polypropionate natural products. Anti methylations of the above epoxides are possible by either the reaction of methyl organometallics promoted by copper(I), or via reaction with trimethylaluminum to yield stereotetrads 11, 12, 22, and 24. Syn methylations are achieved via Lawton SN2‘ reaction in the case of stereotetrads 10, 15, and 38, while stereotetrad 13 is accessed by an oxidation/reduction alcohol inversion sequence from stereotetrad 11. All stereotetrads were obtained in high diastereomeric ratios and yields, and their relative stereochemistry was confirmed by X-ray crystallography. Oxidative cleavage of the cyclic stereotetrads yields termini-differentiated acyclic heptanyl stereotetrads ready for use in building larger fragments in the course of target syntheses

Designer Discodermolide Segments via Ozonolysis of Vinyl Phosphonates

To apply our collection of enantiopure 7-ring vinyl sulfones to probe the anticancer SAR of a series of computer-designed (+)-discodermolide analogs, the ozonolytic reactivity of transposed cyclic vinyl phosphonates was explored. Successful preparation of the desired aldehyde-esters and lactones from vinyl phosphonates via an oxidative cleavage−phosphite/methanol exchange sequence is described