Increased use of enzymes producing chiral amines
A research group at the University of Tokyo has demonstrated the mechanism by which an enzyme used in industrial production of an important drug for type-2 diabetes recognizes its target. This finding will further design of novel biocatalysts for industrial production of chiral amine compounds, crucial building blocks in the synthesis of some pharmaceutical drugs.
Pure chiral amines are crucial building blocks in the synthesis of some pharmaceutical drugs, agrochemicals and other chemical compounds. Amine transaminases (ATAs) are the focus of increasing attention as useful tools for efficient chiral-amine production. In particular, R-stereospecific ATA (R-ATA), a type of ATA that produces only R-chiral amines, has great commercial value.
In 2010 two US pharmaceutical companies created a variant of an R-ATA allowing industrial-scale synthesis of sitagliptin, a medicine for type-2 diabetes. The improved enzyme gave a 53% increase in daily production volume and a 19% reduction in total cost, as compared to the chemical approach conventionally used to synthesize sitagliptin.
However, how the industrially-important enzyme R-ATA recognized its substrate and other details remained unclear.
The research group of Professor Masaru Tanokura at the Graduate School of Agricultural and Life Sciences of the University of Tokyo, in collaboration with Biotechnology and Development Laboratories of Kaneka Corporation, determined the crystal structures of R-ATA from a bacteria that lives in soil and other materials, Arthrobacter sp. KNK168 (Ab-R-RTA), and demonstrated the mechanism of the substrate recognition and substrate specificity of R-ATAs.
One unique characteristic of ATAs is that they recognize two different substrates in the same active site, and it was found that the active-site residue arginine (Arg138) functions on both substrates. Moreover, the structures of an artificial R-ATA and the G136F mutant of Ab-R-ATA (created by substituting the 136th base glycine for phenylalanine) revealed that a loop near the catalytic site was the target site that allowed the change in substrate specificity.
“These findings should lead to the rational design of R-ATAs based on this structural information to develop novel biocatalysts useful for the production of a diverse range of chiral amine compounds. This would accelerate the industrial uses of chiral-amine synthesis using R-ATAs,” says Professor Tanokura.
*Superimposed dimeric structures of Ab-R-ATA and ATA-117-Rd11. One protomer of the dimer is shown in surface representation (right) and the other is drawn as a ribbon diagram (left). The loops near the active sites of Ab-R-ATA and ATA-117-Rd11 are highlighted in orange and green, respectively, clearly showing the difference in structure.
UTokyo Research article
Euan McKay | ResearchSea
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences