Efficient Conversion of Acetate to 3-Hydroxypropionic Acid by Engineered Escherichia coli

Acetate, which is an abundant carbon source, is a potential feedstock for microbial processes that produce diverse value-added chemicals. In this study, we produced 3-hydroxypropionic acid (3-HP) from acetate with engineered Escherichia coli. For the efficient conversion of acetate to 3-HP, we initially introduced heterologous mcr (encoding malonyl-CoA reductase) from Chloroflexus aurantiacus. Then, the acetate assimilating pathway and glyoxylate shunt pathway were activated by overexpressing acs (encoding acetyl-CoA synthetase) and deleting iclR (encoding the glyoxylate shunt pathway repressor). Because a key precursor malonyl-CoA is also consumed for fatty acid synthesis, we decreased carbon flux to fatty acid synthesis by adding cerulenin. Subsequently, we found that inhibiting fatty acid synthesis dramatically improved 3-HP production (3.00 g/L of 3-HP from 8.98 g/L of acetate). The results indicated that acetate can be used as a promising carbon source for microbial processes and that 3-HP can be produced from acetate with a high yield (44.6% of the theoretical maximum yield).11Ysciescopu

Photometric Selection of Unobscured QSOs in the Ecliptic Poles: KMTNet in the South Field and Pan-STARRS in the North Field

We search for quasi-stellar objects (QSOs) in a wide area of the south ecliptic pole (SEP) field, which has been and will continue to be intensively explored through various space missions. For this purpose, we obtain deep broadband optical images of the SEP field covering an area of $\sim$$14.5\times14.5$ deg$^2$ with the Korea Microlensing Telescope Network. The 5$\sigma$ detection limits for point sources in the $BVRI$ bands are estimated to be $\sim$22.59, 22.60, 22.98, and 21.85 mag, respectively. Utilizing data from Wide-field Infrared Survey Explorer, unobscured QSO candidates are selected among the optically point-like sources using the mid-infrared (MIR) and optical-MIR colors. To further refine our selection and eliminate any contamination not adequately removed by the color-based selection, we perform the spectral energy distribution fitting with archival photometric data ranging from optical to MIR. As a result, we identify a total of 2,383 unobscured QSO candidates in the SEP field. We also apply a similar method to the north ecliptic pole field using the Pan-STARRS data and obtain a similar result of identifying 2,427 candidates. The differential number count per area of our QSO candidates is in good agreement with those measured from spectroscopically confirmed ones in other fields. Finally, we compare the results with the literature and discuss how this work will be implicated in future studies, especially with the upcoming space missions.Comment: 14 pages, 9 figures, accepted for publication in ApJ

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Development of synthetic microbial consortium for efficient conversion of non-fermentable substrates to 3-hydroxypropionic acid

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Improving enzymatic conversion of water insoluble substrate using bicontinuous interfacially jammed emulsion gels (BIJEL)

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