biostudies-literatureUnknown3(5)Klein JSynthetic 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 tACS synthetic biology314-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC4046787biostudies-literatureYeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery.PMC4046787Boussemghoune THeal JRTange TOHeim JHamilton WDHatsch AKlein JJaeschke GDelegrange FfalseYeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery.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 t2014-01-01T00:00:00Z2014 May2026-05-03T11:07:51.3Z2019-03-27T01:29:31ZS-EPMC40467872474211510.1021/sb400177x