{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["108(33)"],"submitter":["Morita H"],"pubmed_abstract":["HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide-alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or 6.6.5.6-fused) ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C?C and C?N bond formation to generate the novel polyketide-alkaloid scaffold."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["13504-9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3158201"],"repository":["biostudies-literature"],"pubmed_title":["Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase."],"pmcid":["PMC3158201"],"pubmed_authors":["Kondo S","Kohno T","Shi SP","Sugio S","Morita H","Wakimoto T","Kato R","Yamashita M","Abe I"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase.","description":"HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide-alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or 6.6.5.6-fused) ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C?C and C?N bond formation to generate the novel polyketide-alkaloid scaffold.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Aug","modification":"2020-11-19T15:58:30Z","creation":"2019-03-27T00:14:14Z"},"accession":"S-EPMC3158201","cross_references":{"pubmed":["21825160"],"doi":["10.1073/pnas.1107782108"]}}