Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an...Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an oak tree.Teucrium species are prolific producers of diterpenes,endowing them with valuable properties widely utilized in traditional and modern medicine.Sequencing and assembly of the 3-Gbp tetraploid T.chamaedrys genome revealed 74 diterpene synthase genes,with a substantial number of these genes clustered at four synteny genomic loci,each harboring a copy of a large diterpene biosynthetic gene cluster.Comparative genomics revealed that this cluster is conserved in the closely related species Teucrium marum.Along with the presence of several cytochrome p450 sequences,this region is among the largest biosynthetic gene clusters identified.Teucrium is well known for accumulating clerodane-type diterpenoids,which are produced from a kolavenyl diphosphate precursor.To elucidate the complex biosynthetic pathways of these medicinal compounds,we identified and functionally characterized several kolavenyl diphosphate synthases from T.chamaedrys.The remarkable chemical diversity and tetraploid nature of T.chamaedrys make it a valuable model for studying genomic evolution and adaptation in plants.展开更多
Researchers have uncovered hundreds of thousands of natural products,many of which contribute to med-icine,materials,and agriculture.However,missing knowledge about the biosynthetic pathways of these products hinders ...Researchers have uncovered hundreds of thousands of natural products,many of which contribute to med-icine,materials,and agriculture.However,missing knowledge about the biosynthetic pathways of these products hinders their expanded use.Nucleotide sequencing is key to pathway elucidation efforts,and an-alyses of the molecular structures of natural products,although seldom discussed explicitly,also play an important role by suggesting hypothetical pathways for testing.Structural analyses are also important in drug discovery,for which many molecular representation systems—methods of representing molecular structures in a computer-friendly format—have been developed.Unfortunately,pathway elucidation inves-tigations seldom use these representation systems.This gap likely occurs because those systems are pri-marily built to document molecular connectivity and topology rather than the absolute positions of bonds and atoms in a common reference frame,which would enable chemical structures to be connected with potential underlying biosynthetic steps.Here,we expand on recently developed skeleton-based molecular representation systems by implementing a common-reference-frame-oriented system.We tested this sys-tem using triterpenoid structures as a case study and explored its applications in biosynthesis and struc-tural diversity tasks.The common-reference-frame system can identify structural regions of high or low variability on the scale of atoms and bonds and enable hierarchical clustering that is closely connected to underlying biosynthesis.Combined with information on phylogenetic distribution,the system illuminates distinct sources of structural variability,such as different enzyme families operating in the same pathway.These characteristics outline the potential of common-reference-frame molecular representation systems to support large-scale pathway elucidation efforts.展开更多
基金support of the Neogen Land Grant Prize,an endowed grant program administered by the Office of Research and Innovation at Michigan State University(MSU),which supports graduate students in translating their research into real-world applications that positively impact society and the US economyfunded by a National Science Foundation(NSF)-IMPACTS Training Grant(DGE-1828149)+6 种基金funded by NSF Dimensions of Biodiversity(DEB 1737898)supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM110523the US Department of Energy Great Lakes Bioenergy Research Center Cooperative Agreement DESC0018409funding from the Department of Biochemistry and Molecular Biology at MSU and support from AgBioResearch(MICL02454)supported in part by the National Science Foundation under Grant number 1737898funding from the University of Georgia,the Georgia Research Alliance,and Georgia Seed Developmentsupport from the NSF under grant number ISO-2029959.
文摘Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an oak tree.Teucrium species are prolific producers of diterpenes,endowing them with valuable properties widely utilized in traditional and modern medicine.Sequencing and assembly of the 3-Gbp tetraploid T.chamaedrys genome revealed 74 diterpene synthase genes,with a substantial number of these genes clustered at four synteny genomic loci,each harboring a copy of a large diterpene biosynthetic gene cluster.Comparative genomics revealed that this cluster is conserved in the closely related species Teucrium marum.Along with the presence of several cytochrome p450 sequences,this region is among the largest biosynthetic gene clusters identified.Teucrium is well known for accumulating clerodane-type diterpenoids,which are produced from a kolavenyl diphosphate precursor.To elucidate the complex biosynthetic pathways of these medicinal compounds,we identified and functionally characterized several kolavenyl diphosphate synthases from T.chamaedrys.The remarkable chemical diversity and tetraploid nature of T.chamaedrys make it a valuable model for studying genomic evolution and adaptation in plants.
基金supported by grant no.T32-GM110523 from the National Institute of General Medical Sciences of the National Institutes of HealthD.M.acknowledges funding from an NSF-IMPACTS training grant(DGE-1828149)+1 种基金NSF Dimensions of Biodiversity(DEB 1737898)Jeff Schell Bayer Foundation Fellowship 2022(application no.JS-2022-029).
文摘Researchers have uncovered hundreds of thousands of natural products,many of which contribute to med-icine,materials,and agriculture.However,missing knowledge about the biosynthetic pathways of these products hinders their expanded use.Nucleotide sequencing is key to pathway elucidation efforts,and an-alyses of the molecular structures of natural products,although seldom discussed explicitly,also play an important role by suggesting hypothetical pathways for testing.Structural analyses are also important in drug discovery,for which many molecular representation systems—methods of representing molecular structures in a computer-friendly format—have been developed.Unfortunately,pathway elucidation inves-tigations seldom use these representation systems.This gap likely occurs because those systems are pri-marily built to document molecular connectivity and topology rather than the absolute positions of bonds and atoms in a common reference frame,which would enable chemical structures to be connected with potential underlying biosynthetic steps.Here,we expand on recently developed skeleton-based molecular representation systems by implementing a common-reference-frame-oriented system.We tested this sys-tem using triterpenoid structures as a case study and explored its applications in biosynthesis and struc-tural diversity tasks.The common-reference-frame system can identify structural regions of high or low variability on the scale of atoms and bonds and enable hierarchical clustering that is closely connected to underlying biosynthesis.Combined with information on phylogenetic distribution,the system illuminates distinct sources of structural variability,such as different enzyme families operating in the same pathway.These characteristics outline the potential of common-reference-frame molecular representation systems to support large-scale pathway elucidation efforts.
