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Researchers at the Goethe University have developed a simple model using the nematode Caenorhabditis elegans that can be used to test substances for treating…
Background
Biocatalysts that can perform stereo- and regioselective hydroxylation of steroids are of great interest, since these molecules are among the most strongly marketed compounds of the pharmaceutical industry.
Especially the human metabolites 16-ß-OH-Testosterone and Androstendion are desired products, as they have a wide application as food, dietary supplements and medical products or in terms of diagnostics.
Testosterone can be metabolized by various human microsomal cytochrome P450 systems to the corresponding 16-ß-OH metabolite. So far, these enzymes are not capable of a regio- and stereoselective hydroxylation of testosterone. More than that, mammalian P450 systems are characterized by low stability and activity as well as an unpleasant expression level when compared to bacterial P450 systems.
Invention
Biochemists and pharmaceutical biologists of Saarland University have developed an effective recombinant biotransformation system based on a Bacillus megaterium strain that is capable of performing both stereo- and regioselective hydroxylation of non-activated carbon atoms of testosterone giving rise to 16-ß-OH-Testosterone in one step. The biocatalyst can further be applied in the synthesis of Androstendion using testosterone as a starting material.
Advantages
• Very fast and cost-efficient synthesis of steroid derivatives
• One step transformation of testosterone into 16-ß-OH testosterone
• No side products
• High yield
Background
The biotechnological production of 25-OH Vitamin D3 is of great importance, as this inactivated position 25 within vitamin D3 is hardly achievable by means of organic synthesis, especially in terms of a regio- and stereoselective manner.
Within the human body, 25-OH vitamin D3 is converted into the biological active form of vitamin D3 which is important for the Ca2+ deposit into bones. Furthermore, in case of hepatic cirrhosis, its substitution is essential. It has anti-carcinogenic effects and acts protective in terms of autoimmune and cardiovascular diseases.
25-OH vitamin D3 is also used as a standard in clinical laboratory diagnostics. Altogether, 25-OH vitamin D3 is valuable concerning biotechnology, pharmacy and medicine.
Invention
Biochemists of Saarland University identified and optimized two cytochrome P450 systems which are capable of performing a regio- and stereoselective hydroxylation of vitamin D3 in one step, transferring vitamin D3 to 25-OH and other hydroxyl- derivatives of vitamin D3. The enzymes belong to the CYP109 family.
One of these enzymes is capable of synthesizing 25-OH vitamin D3 as a major product and three side products in vitro producing a yield of 26 mg/l/24h.
The second one gives rise to 25-OH vitamin D3 as the only product producing a yield of 5 mg/l/24h.
Advantages
• Synthesis of 25-OH vitamin D3 and other hydroxyl-derivatives in high yields
o 25-OH vitamin D3 and three side products→ 26 mg/l/24h
o 25-OH vitamin D3 → 5 mg/l/24h
• Low production costs
• No toxic side products as in classical organic synthesis
In freeze substitution the water content in biological samples is replaced with a solvent (usually acetone or methanol) and is a notoriously slow technique. This invention significantly reduces the duration by agitating samples during the process.
Glutathione S-transferase P1 (GSTP1), applied as a recombinant protein, shows powerful longterm cardioprotective effects in a rat model for
myocardial infarction after a single application within 2 hours after infarction.
Biotechnological expression of highly active proteins or small chemical compounds of pharmaceutical relevance is often difficult. Many proteins or molecules of interest (POIs/MOIs) have cytotoxic side effects and interfere with the host’s metabolism. The invention provides a versatile tool – based on a low-temperature inducible protein accumulation system (lt-degron) – and methods to generate so-called ‘phenotypes on demand’ for the production of POIs/MOIs in a spatial and time-dependent manner ensuring proper posttranslational modifications. For the first time, it has been adopted to multicellular organisms like insects and intact plants in vivo.