Application of directed divergent evolution strategy in natural product biosynthesis

Genetic diversity is a result of evolution, enabling multiple ways for one particular physiological activity. Here, we introduce this strategy into bioengineering. We design two hydroxytyrosol biosynthetic pathways using tyrosine as substrate. We show that the synthetic capacity is significantly improved when two pathways work simultaneously comparing to each individual pathway. Next, we engineer flavin-dependent monooxygenase HpaBC for tyrosol hydroxylase, tyramine hydroxylase, and promiscuous hydroxylase active on both tyrosol and tyramine using directed divergent evolution strategy. Then, the mutant HpaBCs are employed to catalyze two missing steps in the hydroxytyrosol biosynthetic pathways designed above. Our results demonstrate that the promiscuous tyrosol/tyramine hydroxylase can minimize the cell metabolic burden induced by protein overexpression and allow the biosynthetic carbon flow to be divided between two pathways. Thus, the efficiency of the hydroxytyrosol biosynthesis is significantly improved by rearranging the metabolic flux among multiple pathways

Methyl (1H-pyrrol-2-ylcarbonyl­amino)acetate

In the crystal structure of the title compound, C8H10N2O3, mol­ecules are linked by N—H⋯O hydrogen bonds, forming ribbons of centrosymmetric dimers extending along the c axis

Electric Field Effect in Multilayer Cr2Ge2Te6: a Ferromagnetic Two-Dimensional Material

The emergence of two-dimensional (2D) materials has attracted a great deal of attention due to their fascinating physical properties and potential applications for future nanoelectronic devices. Since the first isolation of graphene, a Dirac material, a large family of new functional 2D materials have been discovered and characterized, including insulating 2D boron nitride, semiconducting 2D transition metal dichalcogenides and black phosphorus, and superconducting 2D bismuth strontium calcium copper oxide, molybdenum disulphide and niobium selenide, etc. Here, we report the identification of ferromagnetic thin flakes of Cr2Ge2Te6 (CGT) with thickness down to a few nanometers, which provides a very important piece to the van der Waals structures consisting of various 2D materials. We further demonstrate the giant modulation of the channel resistance of 2D CGT devices via electric field effect. Our results illustrate the gate voltage tunability of 2D CGT and the potential of CGT, a ferromagnetic 2D material, as a new functional quantum material for applications in future nanoelectronics and spintronics.Comment: To appear in 2D Material

Coexistence of Logarithmic and SdH Quantum Oscillations in Ferromagnetic Cr-doped Tellurium Single Crystals

We report the synthesis of transition-metal-doped ferromagnetic elemental single-crystal semiconductors with quantum oscillations using the physical vapor transport method. The 7.7 atom% Cr-doped Te crystals (Cr_Te) show ferromagnetism, butterfly-like negative magnetoresistance in the low temperature (< 3.8 K) and low field (< 0.15 T) region, and high Hall mobility, e.g., 1320 cm2 V-1 s-1 at 30 K and 350 cm2 V-1 s-1 at 300 K, implying that Cr_Te crystals are ferromagnetic elemental semiconductors. When B // c // I, the maximum negative MR is -27% at T = 20 K and B = 8 T. In the low temperature semiconducting region, Cr_Te crystals show strong discrete scale invariance dominated logarithmic quantum oscillations when the direction of the magnetic field B is parallel to the [100] crystallographic direction and show Landau quantization dominated Shubnikov-de Haas (SdH) oscillations for B // [210] direction, which suggests the broken rotation symmetry of the Fermi pockets in the Cr_Te crystals. The findings of coexistence of multiple quantum oscillations and ferromagnetism in such an elemental quantum material may inspire more study of narrow bandgap semiconductors with ferromagnetism and quantum phenomena.Comment: 25 pages, 25 figure

Investigation of the causal relationship between inflammatory bowel disease and type 2 diabetes mellitus: a Mendelian randomization study

Background: Type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) have been associated, according to various epidemiological research. This study uses Mendelian randomization (MR) to investigate the causal link between T2DM and IBD.Methods: To investigate the causal relationship between IBD and T2DM risk using European population data from the genome-wide association study (GWAS) summary datasets, we constructed a two-sample MR study to evaluate the genetically predicted impacts of liability towards IBD outcomes on T2DM risk. As instrumental variables (IVs), we chose 26 single nucleotide polymorphisms (SNPs) associated with IBD exposure data. The European T2DM GWAS data was obtained from the IEU OpenGWAS Project database, which contains 298,957 cases as the outcome data. The causal relationship between T2DM and IBD using a reverse MR analysis was also performed.Results: The two-sample MR analysis, with the Bonferroni adjustment for multiple testing, revealed that T2DM risk in Europeans is unaffected by their IBD liability (odds ratio (OR): 0.950–1.066, 95% confidence interval (CI): 0.885–1.019, p = 0.152–0.926). The effects of liability to T2DM on IBD were not supported by the reverse MR analysis either (OR: 0.739–1.131, 95% confidence interval (CI): 0.651–1.100, p = 0.058–0.832). MR analysis of IBS on T2DM also have no significant causal relationship (OR: 0.003–1.007, 95% confidence interval (CI): 1.013–5.791, p = 0.069–0.790). FUMA precisely mapped 22 protein-coding genes utilizing significant SNPs of T2DM acquired from GWAS.Conclusion: The MR study showed that the existing evidence did not support the significant causal effect of IBD on T2DM, nor did it support the causal impact of T2DM on IBD