Publications

A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.

Abstract not Available.

<p>Supplementary Table 2. Sex-Specific Standard Deviations of Body Composition Measurements (CT SMA, DXA ALM, D3Cr Muscle, CT TAT, and DXA TBF)</p>

The structure of interfacial water near suspended graphene electrodes in contact with aqueous solutions of Na₂SO₄, NH₄Cl, and (NH₄)₂SO₄ has been studied using confocal Raman spectroscopy, sum frequency vibrational spectroscopy, and Kelvin probe force microscopy. SO₄^2- anions were found to preferentially accumulate near the interface at an open circuit potential (OCP), creating an electrical field that orients water molecules below the interface, as revealed by the increased intensity of the O-H stretching peak of H-bonded water. No such increase is observed with NH₄Cl at the OCP. The intensity of the dangling O-H bond stretching peak however remains largely unchanged. The degree of orientation of the water molecules as well as the electrical double layer strength increased further when positive voltages are applied. Negative voltages on the other hand produced only small changes in the intensity of the H-bonded water peaks but affected the intensity and frequency of dangling O-H bond peaks. The TOC figure is an oversimplified representation of the system in this work.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The cores of stars are the cosmic furnaces where light elements are fused into heavier nuclei. The fusion of hydrogen to helium initially powers all stars. The ashes of the fusion reactions are then predicted to serve as fuel in a series of stages, eventually transforming massive stars into a structure of concentric shells. These are composed of natal hydrogen on the outside, and consecutively heavier compositions inside, predicted to be dominated by helium, carbon/oxygen, oxygen/neon/magnesium, and oxygen/silicon/sulphur. Silicon and sulphur are fused into inert iron, leading to the collapse of the core and either a supernova explosion or the direct formation of a black hole. Stripped stars, where the outer hydrogen layer has been removed and the internal He-rich layer (in Wolf-Rayet WN stars) or even the C/O layer below it (in Wolf-Rayet WC/WO stars) are exposed, provide evidence for this shell structure, and the cosmic element production mechanism it reflects. The types of supernova explosions that arise from stripped stars embedded in shells of circumstellar material (most notably Type Ibn supernovae from stars with outer He layers, and Type Icn supernovae from stars with outer C/O layers) confirm this scenario. However, direct evidence for the most interior shells, which are responsible for the production of elements heavier than oxygen, is lacking. Here, we report the discovery of the first-of-its-kind supernova arising from a star peculiarly stripped all the way to the silicon and sulphur-rich internal layer. Whereas the concentric shell structure of massive stars is not under debate, it is the first time that such a thick, massive silicon and sulphur-rich shell, expelled by the progenitor shortly before the SN explosion, has been directly revealed.

SUMMARY In combination with advanced mechanistic modeling and the generation of high-quality multi-dimensional data sets, machine learning is becoming an integral part of understanding and engineering living systems. Here we show that mechanistic and machine learning models can complement each other and be used in a combined approach to enable accurate genotype-to-phenotype predictions. We use a genome-scale model to pinpoint engineering targets and produce a large combinatorial library of metabolic pathway designs with different promoters which, once phenotyped, provide the basis for machine learning algorithms to be trained and used for new design recommendations. The approach enables successful forward engineering of aromatic amino acid metabolism in yeast, with the new recommended designs improving tryptophan production by up to 17% compared to the best designs used for algorithm training, and ultimately producing a total increase of 106% in tryptophan accumulation compared to optimized reference designs. Based on a single high-throughput data-generation iteration, this study highlights the power of combining mechanistic and machine learning models to enhance their predictive power and effectively direct metabolic engineering efforts.