Taxol(Paclitaxel)is a diterpene from Taxus species and has been used in treatment of various kinds of cancers.Geranylgeranyl diphosphate synthase(GGPPS)catalyzes the formation of geranylgeranyl diphosphate(GGPP,the co...Taxol(Paclitaxel)is a diterpene from Taxus species and has been used in treatment of various kinds of cancers.Geranylgeranyl diphosphate synthase(GGPPS)catalyzes the formation of geranylgeranyl diphosphate(GGPP,the common precursor for diterpenes and plays a key role in taxol biosynthesis.Here we report a functional GGPPS gene from Taxus chinensis(designated TcGGPPS).TcGGPPS is an intron free gene and has a 1,182-bp open reading frame encoding a polypeptide of 393 amino acid residues with a calculated molecular mass of 42.63 kDa and an isoelectric point of 5.58.The catalytic activity of TcGGPPS for production of GGPP was verified by a color enhancement assay in the Escherichia coli cells harboring plasmid pAC-BETA.Multiple sequence alignment indicates that TcGGPPS is a little different in sequence from the functional GGPPS genes from other Taxus species such as T.canadensis,T.media and T.wallichiana,which are almost identical to each other.Protein structure prediction by using bioinformatics reveals that TcGGPPS consists of 52.2%α-helix,10.9%extended strand,8.4%β-turn and 28.5%random coil,and has a three-dimensional structure highly similar to the structurally known Sinapis alba GGPPS.In silicon predictions also demonstrate that TcGGPPS has a plastid-targeting peptide at the N-terminus,suggesting it is responsible for the synthesis of GGPP in plastids.展开更多
Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help pred...Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’responses.As particular self-amplifying biotherapeutics,the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication.By using weighted gene co-expression network analysis(WGCNA),we found matrix remodeling associated 8(MXRA8)is positively correlated with the oncolysis induced by oncolytic virus M1(OVM).展开更多
文摘Taxol(Paclitaxel)is a diterpene from Taxus species and has been used in treatment of various kinds of cancers.Geranylgeranyl diphosphate synthase(GGPPS)catalyzes the formation of geranylgeranyl diphosphate(GGPP,the common precursor for diterpenes and plays a key role in taxol biosynthesis.Here we report a functional GGPPS gene from Taxus chinensis(designated TcGGPPS).TcGGPPS is an intron free gene and has a 1,182-bp open reading frame encoding a polypeptide of 393 amino acid residues with a calculated molecular mass of 42.63 kDa and an isoelectric point of 5.58.The catalytic activity of TcGGPPS for production of GGPP was verified by a color enhancement assay in the Escherichia coli cells harboring plasmid pAC-BETA.Multiple sequence alignment indicates that TcGGPPS is a little different in sequence from the functional GGPPS genes from other Taxus species such as T.canadensis,T.media and T.wallichiana,which are almost identical to each other.Protein structure prediction by using bioinformatics reveals that TcGGPPS consists of 52.2%α-helix,10.9%extended strand,8.4%β-turn and 28.5%random coil,and has a three-dimensional structure highly similar to the structurally known Sinapis alba GGPPS.In silicon predictions also demonstrate that TcGGPPS has a plastid-targeting peptide at the N-terminus,suggesting it is responsible for the synthesis of GGPP in plastids.
基金We acknowledge Dr.Zhe Liu of the Guangdong Provincial Center for Disease Control and Prevention for his assistance with cryo-EM.Miss.Liumei Wu and Miss.Jing Tang assisted with transfection assay and RNA-scope assay.This work was supported by the National Natural Science Foundation of China(No.81973342,82073883,81772675,81903652,and 81802536)the National Key R&D Program of China(2021YFA0909800)the Science and Technology Program of Guangzhou(No.201707020003).
文摘Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’responses.As particular self-amplifying biotherapeutics,the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication.By using weighted gene co-expression network analysis(WGCNA),we found matrix remodeling associated 8(MXRA8)is positively correlated with the oncolysis induced by oncolytic virus M1(OVM).
