ETH-Zürich: Stirring device and enzymatic synthesis route to license

Two Licensing Opportunities

Scientists at the Swiss Federal Institute of Technology Zurich (ETH-Zurich) have developed two new inventions which are now available for licensing.  The first is a rotating stirring device with a narrow distribution of energy dissipation rate for use in biochemical or bioreaction processes.  The second is an enzymatic synthesis route to produce β-Peptides and L-Carnosine, an environmentally friendly method to produce L-Carnosine with pharmaceutical potential.  Both inventions are available for licensing.

Rotating Stirring Device with Substantially Narrow Distribution of Energy Dissipation Rate

The rotating stirring device of the present invention comprises an outer member (e.g. a cylinder) and a preferably concentrically mounted inner member. The present invention utilizes the principle of applying non-constant gap width between an inner and an outer member in the Taylor Couette (TC) device in order to reduce or completely destroy the Taylor vortices in the TC device, as a result, to obtain a substantially narrow distribution of energy dissipation rate within the gap. The non-constant gap width in this invention is realized by using a non-circular cross-section for the inner member of the TC device along the radial direction perpendicular to the rotation axis. The cross-section of the inner member perpendicular to the rotation axis can be any type of equilateral or inequilateral polygons with curved cusps. Typical examples for the cross-section shape of the inner member are: elliptical, triangle, rectangular, square, etc.

Main Advantages

Such device is particularly advantageous as a reactor or mixer for processes where chemical and physical properties are sensitive to the variations in the shear rate and for processes that involve fragile components.

The device can also be used to replace the Taylor Couette device for the purposes of improving mass transfer and of avoiding separation of components in the gap in the case of presence of differences in density among components.

Field of Application

• Biochemical or Bioreaction processes
• Single or Multiple phase reaction
• Mixing processes
• Polymerization or copolymerization process of monomers and/or oligomers
• Granulation and/or coagulation process of colloidal systems (e.g. polymer latexes, waste water treatment, protein colloids in dairy industry, etc.).

Patent Status

• EP granted
• US pending

Background

Mechanically stirred tank (ST) reactors are widely used for processes that require continuous mixing of various components and efficient mass exchange between different phases (e.g. gas-liquid, gas-liquid-solid, liquid-liquid, liquid-solid, etc.). A common shortcoming of the ST reactors is a broad distribution of the energy dissipation rate in the mass contained in the reactors, which is undesired for processes that are sensitive to the local energy dissipation rate. For example, when the reaction kinetics of a polymerization process is sensitive to the local energy dissipation rate, a broad distribution of the energy dissipation rate in the reactor may lead to a broad distribution of molecular weight.

For a bio-reaction process, when the distribution of the energy dissipation rate is broad, the large energy dissipation rates in the tail of the distribution lead to large turbulent shear rate, which can damage the bio-cells contained in the system. Thus, in the present invention, a new type of rotating stirring device is described, which generates a substantially narrow distribution of energy dissipation rate. The invented devices are particularly suitable for processes that require a homogeneous turbulent flow environment and involving fragile components.

Ref. No. T-03-023

Three bacterial β-aminopeptidases that catalyze the hydrolysis and synthesis of peptides containing N-terminal β-amino acids are applied in the production of Carnosine and a variety of β-peptides. The enzymes origin from Sphingosinicella xenopeptidilytica

3-2W4, S. microcystinivorans Y2 and Ochrobactrum anthropi and are named 3-2W4 BapA, Y2 BapA and DmpA, respectively. These hydrolases belong to the very few enzymes that react with structures containing β-amino acids and they are the only known and characterized peptidases that are able to synthesize β- and mixed β,α-peptides. This exclusive feature allows the biocatalytical production of a variety of different di-, tri- and oligopeptides that contain β-amino acids. The biotechnological procedure has the advantage of mild reaction conditions such as moderate temperatures and pure aqueous media. Hence, the application of β-aminopeptidases provides a potentially economical and ecological alternative for the synthesis of β-amino acid containing peptides.

Special emphasis was placed on the synthesis of Carnosine and the optimization of the reaction conditions of this valuable food additive or anti aging product.

Main Advantages

• Mild method to produce L-Carnosine
• Method with potential to create new and potentially interesting β-Peptides
• Environmentally friendly process
• Reaction temperature at 37°C
• Enzymes stable under reaction conditions
• Long term storage possible (lyophilized)
• Enzyme expression systems available

Field of Application

Catalyst − β-Aminopeptidases:

• A pool of potentially interesting new β-Peptides can be synthesized
• Good potential for up-scaling
• Cost-effective and ecological process
• Exclusive substrate specificity

Product - L-Carnosine:

• Anti-aging - Food supplement
• Positive effect on Diabetes II
• Stomach stabilizing effect as Zinc-complex

Product - β–Peptides:

• Chiral peptides with high potential as pharmaceuticals or pharmaceutical intermediates
• Anti wrinkling compound – Cosmetic applications

Patent Status

• Patent pending

Background

β-Peptides consisting of β-amino acids with proteinogenic side chains were chemically synthesized for the first time in 1996 and do not occur in nature.

This class of compounds exhibits unexpected properties, such as high metabolic stability and the ability to adopt stable secondary structures. Due to these characteristics, they act as peptidomimetics and are considered to be pharmaceutically interesting agents.

One natural dipeptide that contains a β-amino acid is Carnosine. Several studies support Carnosine`s diverse positive impacts on human health such as anti-oxidative and antiglycating properties as well as effects on the sugar metabolism of diabetic patients. It is sold as a dietary supplement and a growing market is observed.

So far, only chemical synthesis routes have been described for the production of β-peptides and mixed β,α-peptides. The synthesis of β-peptides is usually performed using adapted methods from the classical repertoire of peptide synthesis, whereas Carnosine is routinely synthesized by other chemical methods such as one- or two-step procedures that involve organic solvents, heavy metals and strong bases.

Ref. Eaw-001