The Strategy - From Natural Product Screening to Lead Optimisation

With its large strain collection of cyanobacteria and its Know-How based on more than 20 years of academic cyanobacterial research at the Humboldt University Berlin, Cyano Biotech is aiming to identify novel biologically active lead compounds.

To date more than 800 cyanobacterial nonribosomally formed peptides, polyketides and hybrids of these two major products are known, many of which possess pharmacologically interesting features. As outlined in the figure Cyano Biotech employs two different routes to identify novel lead compounds.

One strategy aims at the identification of new compounds by screening cyanobacteria grown under diverse culture conditions. Unlike other microbial producers cyanobacteria display an enormous range of closely related structural variants of bioactive compounds. Thus enhancing the possibility that, once a lead compound has been identified, more potent analogues thereof, with improved characteristics, can be found by screening related strains. This in turn considerably minimises the need for chemical modification for a given lead-substance. As it can be assumed that only a small fraction of cyanobacterial species has been identified an intensive screening should lead to the discovery of more species and in particular more closely related strains producing similar compounds.

A second, complementary approach towards the generation of new lead compounds is the creation of so called “unnatural” natural products in cyanobacteria through the targeted alteration of their biosynthetic pathways governing natural products biosynthesis. Cyano Biotech’s platform technologies enable both the specific and non-specific combinatorial biosynthesis of bioactive natural products. The company is currently applying this technology to the pathways for two potentially clinically useful natural products from cyanobacteria, microginin, a highly potent ACE-inhibitor and microcystin, a potent hepatotoxic compound.

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