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Reference: Klein J, et al. (2014) Yeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery. ACS Synth Biol 3(5):314-23

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Abstract

Synthetic biology has been heralded as a new bioengineering platform for the production of bulk and specialty chemicals, drugs, and fuels. Here, we report for the first time a series of 74 novel compounds produced using a combinatorial genetics approach in baker's yeast. Based on the concept of "coevolution" with target proteins in an intracellular primary survival assay, the identified, mostly scaffold-sized (200-350 MW) compounds, which displayed excellent biological activity, can be considered as prevalidated hits. Of the molecules found, >75% have not been described previously; 20% of the compounds exhibit novel scaffolds. Their structural and physicochemical properties comply with established rules of drug- and fragment-likeness and exhibit increased structural complexities compared to synthetically produced fragments. In summary, the synthetic biology approach described here represents a completely new, complementary strategy for hit and early lead identification that can be easily integrated into the existing drug discovery process.

Reference Type
Journal Article
Authors
Klein J, Heal JR, Hamilton WD, Boussemghoune T, Tange TO, Delegrange F, Jaeschke G, Hatsch A, Heim J
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