Process development – Natural compounds

W42 is working on a process development (fermentation/purification) of selected natural compounds.

Actual projects:

ActinomycinX2(V) and ActinomycinD: The actinomycins are chromopeptide lactones produced by various Streptomyces strains. They consist of a phenoxazinone chromophore (actinocin) with two pentapeptide lactone rings attached in amide linkage. The various naturally occurring actinomycins differ by amino acid substitutions in specific positions of their peptide chains, while the actinocin moiety remains unchanged. Due to the planar structure of actinocin, actinomycins can intercalate into GC-rich DNA. This leads to inhibition of transcription in both prokaryotes and eukaryotes. Actinomycins have strong antineoplastic activities, which have attracted much interest in their chemistry and biosynthesis. The high toxicity of the compounds, however, has restricted their therapeutic use to only a few tumor types. Potential application as pay-load for “antibody drug conjugate” approach. Samples for Actinomycin X2 and D are available (purity >90% by HPLC).


Nikkomycin Z: Competitive inhibitor of the chitin synthase an essential enzyme of fungi and insects, because of structural similarity to UDP-N-acetylglucosamine, the building block of chitin. Nik-Z has been found to be effective in vitro and in vivo against some extracellular and intracellular fungal pathogens. Nik-Z is well tolerated (no side effects known), and easily degradable. Potential applications are treatment of fungal infections (pharma), but also the sharply rising infections of plants.


Erythromycin: PKS antibiotic useful for the treatment of a number of bacterial infections. Industrial process for several g/l is available.


Rifamycin W: The rifamycins are a group of antibiotics that are synthesized naturally by different strains of the bacterium Amycolatopsis sp. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections. The Rifamycin W high-producer strain is used as tool for rational strain improvement project, based on the rational use of micro-particles. Samples of enriched Rifamycin W are available.


Cephalosporin C: Cephalosporin C (CPC), is one of the major precusors of β-lactam antibiotics. β-lactam antibiotics are the major first line anti-microbial agents. CPC and its semi-synthetic derivatives play important roles in the pharmaceutical industry. Strains and process for CPC production (>30 g/l) are available.

 

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