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1. SNP by SNP by environment interaction network of alcoholism

   https://doi.org/10.1186/s12918-017-0403-7  

   Zollanvari, Amin; Alterovitz, Gil (March 2017, BMC Systems Biology)
2. Pyruvate Production by Escherichia coli by Use of Pyruvate Dehydrogenase Variants

   https://doi.org/10.1128/AEM.00487-21  

   Moxley, W. Chris; Eiteman, Mark A. (June 2021, Applied and Environmental Microbiology)

   Atomi, Haruyuki (Ed.)

   ABSTRACT Altering metabolic flux at a key branch point in metabolism has commonly been accomplished through gene knockouts or by modulating gene expression. An alternative approach to direct metabolic flux preferentially toward a product is decreasing the activity of a key enzyme through protein engineering. In Escherichia coli , pyruvate can accumulate from glucose when carbon flux through the pyruvate dehydrogenase complex is suppressed. Based on this principle, 16 chromosomally expressed AceE variants were constructed in E. coli C and compared for growth rate and pyruvate accumulation using glucose as the sole carbon source. To prevent conversion of pyruvate to other products, the strains also contained deletions in two nonessential pathways: lactate dehydrogenase ( ldhA ) and pyruvate oxidase ( poxB ). The effect of deleting phosphoenolpyruvate synthase ( ppsA ) on pyruvate assimilation was also examined. The best pyruvate-accumulating strains were examined in controlled batch and continuous processes. In a nitrogen-limited chemostat process at steady-state growth rates of 0.15 to 0.28 h −1 , an engineered strain expressing the AceE[H106V] variant accumulated pyruvate at a yield of 0.59 to 0.66 g pyruvate/g glucose with a specific productivity of 0.78 to 0.92 g pyruvate/g cells·h. These results provide proof of concept that pyruvate dehydrogenase complex variants can effectively shift carbon flux away from central carbon metabolism to allow pyruvate accumulation. This approach can potentially be applied to other key enzymes in metabolism to direct carbon toward a biochemical product. IMPORTANCE Microbial production of biochemicals from renewable resources has become an efficient and cost-effective alternative to traditional chemical synthesis methods. Metabolic engineering tools are important for optimizing a process to perform at an economically feasible level. This study describes an additional tool to modify central metabolism and direct metabolic flux to a product. We have shown that variants of the pyruvate dehydrogenase complex can direct metabolic flux away from cell growth to increase pyruvate production in Escherichia coli . This approach could be paired with existing strategies to optimize metabolism and create industrially relevant and economically feasible processes. 

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3. Learning the statistics of pronoun reference: By word or by category?

   https://doi.org/10.1016/j.cognition.2023.105546  

   Ye, Yining; Arnold, Jennifer E. (October 2023, Cognition)
4. Synthesis of Allenes by Hydroalkylation of 1,3-Enynes with Ketones Enabled by Cooperative Catalysis

   https://doi.org/10.1021/jacs.3c08151  

   Eaton, Maxwell; Dai, Yuping; Wang, Ziyong; Li, Bo; Lamine, Walid; Miqueu, Karinne; Liu, Shih-Yuan (October 2023, Journal of the American Chemical Society)
5. Reduction of Substrates by Nitrogenases

   https://doi.org/10.1021/acs.chemrev.9b00556  

   Seefeldt, Lance C.; Yang, Zhi-Yong; Lukoyanov, Dmitriy A.; Harris, Derek F.; Dean, Dennis R.; Raugei, Simone; Hoffman, Brian M. (March 2020, Chemical Reviews)

   Nitrogenase is the enzyme that catalyzes biological N2 reduction to NH3. This enzyme achieves an impressive rate enhancement over the uncatalyzed reaction. Given the high demand for N2 fixation to support food and chemical production and the heavy reliance of the industrial Haber–Bosch nitrogen fixation reaction on fossil fuels, there is a strong need to elucidate how nitrogenase achieves this difficult reaction under benign conditions as a means of informing the design of next generation synthetic catalysts. This Review summarizes recent progress in addressing how nitrogenase catalyzes the reduction of an array of substrates. New insights into the mechanism of N2 and proton reduction are first considered. This is followed by a summary of recent gains in understanding the reduction of a number of other nitrogenous compounds not considered to be physiological substrates. Progress in understanding the reduction of a wide range of C-based substrates, including CO and CO2, is also discussed, and remaining challenges in understanding nitrogenase substrate reduction are considered. 

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