Contract Fermentation and Natural Products

Contract fermentation and natural products

pellet-ferm-picture-for-websiteThere is renewed interest in natural products as a source of chemical entities, either through discovery of new scaffolds or re-evaluating previously discovered bioactive chemicals.

Hypha has extensive experience in all aspects of natural products chemistry, spanning microbial strain handling, fermentation, yield improvement, through to the purification and structure elucidation of the target compounds. We work flexibly with clients to provide any aspect required, including the production and scale-up of stable and radiolabelled metabolites and natural products. We are able to supply milligram to gram amounts of compounds and have access to multi-thousand litre scale reactors via an alliance with a fermentation provider.

Examples of projects we have undertaken

  • Acquisition, maintenance and fermentation of microbial strains
  • Strain improvement and fermentation optimisation
  • Purification and structure elucidation of complex natural products
  • Production of natural product scaffolds for semi-synthetic modification
  • Production and purification of ADC-payloads and purification of bioactive molecules from mixtures
  • Production of stable isotope-labelled drug metabolites and natural products
  • Production of 3H or 14C radiolabelled difficult-to-synthesise metabolites and natural products, jointly with our partner Selcia

Production of 14C-labelled microbial natural products

Hypha’s microbial and Selcia’s radiochemistry expertise permits production of [14C]-enriched semisynthetic and natural products via isotopically-labelled precursor feeding. The first step involves sourcing and fermenting the microorganism to achieve acceptable yields of the product.
Incorporation of an externally fed [13C]-labelled biosynthetic precursor to a fermentation is then undertaken, with confirmation of the location and extent of uptake of the [13C] label. The process can then be replicated in Selcia’s facility to incorporate a synthesised [14C]-labelled precursor into the final natural product.

Case study— Collaborative project to supply radiolabelled rapamycin
Rapamycin is a microbial product of Streptomyces rapamycinicus and has potent immunosuppressive and anti-proliferative properties. Pilot work was successfully undertaken by Hypha to provide an optimised fermentation process for incorporation of [13C] labelled L-pipecolic acid into rapamycin. The process was then transferred to Selcia for production and purification of the [14C] labelled rapamycin from single labelled [14COOH] L-pipecolic acid, synthesised by Selcia using a short, efficient synthesis from [14C] CO2. A total of 33mg of [14C] rapamycin was purified at Selcia with a radiochemical and chemical purity of 94%, and a specific activity of 16.3 mCi/mmol.

More information

Why work with us?

  • Our track record in natural products. Our client base of pharmaceutical and agrochemical multinationals and SMEs, is testament to our expertise in fermentation, purification, identification and biotransformation of small molecules.
  • Cost effective, flexible service. Clients may outsource entire programs or choose to work with us on a modular basis.  We can also troubleshoot and rework existing processes and provide a full handover to clients.
  • Our processes are scalable. Target molecules can be produced for further work from mg amounts to assess bioactivity, up to g scale and beyond for semi-synthetic modification.

Contact us to discuss how we can help your project succeed.

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