Novel synthetic co‐culture of Acetobacterium woodii and Clostridium drakei using CO2 and in situ generated H2 for the production of caproic acid via lactic acid

Abstract Acetobacterium woodii is known to produce mainly acetate from CO2 and H2, but the production of higher value chemicals is desired for the bioeconomy. Using chain‐elongating bacteria, synthetic co‐cultures have the potential to produce longer‐chained products such as caproic acid. In this study, we present first results for a successful autotrophic co‐cultivation of A. woodii mutants and a Clostridium drakei wild‐type strain in a stirred‐tank bioreactor for the production of caproic acid from CO2 and H2 via the intermediate lactic acid. For autotrophic lactate production, a recombinant A. woodii strain with a deleted Lct‐dehydrogenase complex, which is encoded by the lctBCD genes, and an inserted D‐lactate dehydrogenase (LdhD) originating from Leuconostoc mesenteroides, was used. Hydrogen for the process was supplied using an All‐in‐One electrode for in situ water electrolysis. Lactate concentrations as high as 0.5 g L–1 were achieved with the AiO‐electrode, whereas 8.1 g L–1 lactate were produced with direct H2 sparging in a stirred‐tank bioreactor. Hydrogen limitation was identified in the AiO process. However, with cathode surface area enlargement or numbering‐up of the electrode and on‐demand hydrogen generation, this process has great potential for a true carbon‐negative production of value chemicals from CO2

Identification and Experimental Characterization of an Extremophilic Brine Pool Alcohol Dehydrogenase from Single Amplified Genomes

Because only 0.01% of prokaryotic genospecies can be cultured and <i>in situ</i> observations are often impracticable, culture-independent methods are required to understand microbial life and harness potential applications of microbes. Here, we report a methodology for the production of proteins with desired functions based on single amplified genomes (SAGs) from unculturable species. We use this method to resurrect an alcohol dehydrogenase (ADH/D1) from an uncharacterized halo-thermophilic archaeon collected from a brine pool at the bottom of the Red Sea. Our crystal structure of 5,6-dihydroxy NADPH-bound ADH/D1 combined with biochemical analyses reveal the molecular features of its halo-thermophily, its unique habitat adaptations, and its possible reaction mechanism for atypical oxygen activation. Our strategy offers a general guide for using SAGs as a source for scientific and industrial investigations of “microbial dark matter.

Glioblastoma hijacks neuronal mechanisms for brain invasion

Glioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other subpopulations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease. Tumor cell invasion resembled neuronal migration mechanisms and adopted a Lévy-like movement pattern of probing the environment. Neuronal activity induced complex calcium signals in glioblastoma cells followed by the de novo formation of TMs and increased invasion speed. Collectively, superimposing molecular and functional single-cell data revealed that neuronal mechanisms govern glioblastoma cell invasion on multiple levels. This explains how glioblastoma’s dissemination and cellular heterogeneity are closely interlinked