更新于：2024-11-01

GGPS1

更新于：2024-11-01

基本信息

别名

(2E,6E)-farnesyl diphosphate synthase、Dimethylallyltranstransferase、Farnesyl diphosphate synthase

+ [9]

简介

Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.

关联

项与 GGPS1 相关的药物

AIM-1290

靶点

FDPS x GGPS1

作用机制

FDPS抑制剂 [+1]

在研机构

Takeda Pharmaceutical Co., Ltd. [+1]

原研机构

Stanford University

在研适应症

恶性疟

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

RB-07-16

靶点

GGPS1

作用机制

GGPS1抑制剂

在研机构

McGill University

原研机构

McGill University

在研适应症

多发性骨髓瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CN118121703

专利挖掘

靶点

GGPS1

作用机制-

在研机构

中国医学科学院皮肤病医院

原研机构

中国医学科学院皮肤病医院

在研适应症

内分泌与代谢疾病 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GGPS1 相关的临床结果

登录后查看更多信息

100 项与 GGPS1 相关的转化医学

登录后查看更多信息

0 项与 GGPS1 相关的专利（医药）

登录后查看更多信息

805

项与 GGPS1 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Isolation and characterisation of sesquiterpene synthase from aromatic orchid Phalaenopsis bellina (Rchb.f.) Christenson

Article

作者: Rusdi, Nor Azizun ; Mus, Ahmad Asnawi ; Kumar, Vijay ; Gansau, Jualang Azlan

BACKGROUNDPhalaenopsis bellina, an orchid native to Borneo, is renowned for its unique appearance. It releases distinct fragrances, which have been linked to the presence of terpenoids. However, the identification and study of sesquiterpene synthase in P. bellina remain limited. In this study, we examines the functional characterisation of terpene synthase (TPS) from P. bellina, known as PbTS, through recombinant protein expression and its manifestation in the flower.METHODS AND RESULTSGene annotation of PbTS revealed that the inferred peptide sequence of PbTS comprises 1,680 bp nucleotides encoding 559 amino acids with an estimated molecular mass of 65.2 kDa and a pI value of 5.4. A similarity search against GenBank showed that PbTS shares similarities with the previously published partial sequence of P. bellina (ABW98504.1) and Phalaenopsis equestris (XP_020597359.1 and ABW98503.1). Intriguingly, the phylogenetic analysis places the PbTS gene within the TPS-a group. In silico analysis of PbTS demonstrated stable interactions with farnesyl pyrophosphate (FPP), geranyl pyrophosphate (GPP), and geranylgeranyl pyrophosphate (GGPP). To verify this activity, an in vitro enzyme assay was performed on the PbTS recombinant protein, which successfully converted FPP, GPP, and GGPP into acyclic sesquiterpene β-farnesene, yielding approximately 0.03 mg/L. Expressional analysis revealed that the PbTS transcript was highly expressed in P. bellina, but its level did not correlate with β-farnesene levels across various flowering time points and stages.CONCLUSIONThe insights gained from this study will enhance the understanding of terpenoid production in P. bellina and aid in the discovery of novel fragrance-related genes in other orchid species.

2024-11-16·Natural Product Research

Gibberellic acid 3 enhanced the anticancer activity of Abeliophyllum distichum adventitious roots by activating the diterpenoid biosynthesis pathway

Article

作者: Hyun, Tae Kyung ; Bang, Seoung Gun ; Joeng, Won Tae

The industrial value of various plants has been improved through the of plant cell culture systems with elicitation. In this study, the adventitious root of Abeliophyllum distichum (AdAR) was treated with gibberellic acid 3 (GA3) to improve its anticancer property. The hexane fraction of the GA3-treated A. distichum adventitious root exhibited a stronger cytotoxic activity against A549 cells than the hexane fraction of AdAR. Through GC/MS and principal component analysis, we identified ferruginol and sugiol as anticancer compounds, which were induced by GA3 treatment in AdAR. Gene expression analysis combined with functional characterisation suggests that the GA3 treatment increased the transcription of geranylgeranyl pyrophosphate synthases and copalyl diphosphate synthase, which led to the accumulation of diterpenoids, including ferruginol and sugiol. Overall, these findings can contribute to the advancement of metabolic engineering for enhancing the biosynthesis of active diterpenoids, and facilitate the large-scale production of bioactive compounds sourced from A. distichum.

2024-10-08·Proceedings of the National Academy of Sciences

Engineering substrate channeling in a bifunctional terpene synthase

Article

作者: Marmorstein, Ronen ; Wenger, Eliott S. ; Christianson, David W. ; Schultz, Kollin

Fusicoccadiene synthase from Phomopsis amygdala (PaFS) is a bifunctional terpene synthase. It contains a prenyltransferase (PT) domain that generates geranylgeranyl diphosphate (GGPP) from dimethylallyl diphosphate and three equivalents of isopentenyl diphosphate, and a cyclase domain that converts GGPP into fusicoccadiene, a precursor of the diterpene glycoside Fusicoccin A. The two catalytic domains are connected by a flexible 69-residue linker. The PT domain mediates oligomerization to form predominantly octamers, with cyclase domains randomly splayed out around the PT core. Surprisingly, despite the random positioning of cyclase domains, substrate channeling is operative in catalysis since most of the GGPP generated by the PT remains on the enzyme for cyclization. Here, we demonstrate that covalent linkage of the PT and cyclase domains is not required for GGPP channeling, although covalent linkage may improve channeling efficiency. Moreover, GGPP competition experiments with other diterpene cyclases indicate that the PaFS PT and cyclase domains are preferential partners regardless of whether they are covalently linked or not. The cryoelectron microscopy structure of the 600-kD “linkerless” construct, in which the 69-residue linker is spliced out and replaced with the tripeptide PTQ, reveals that cyclase pairs associate with all four sides of the PT octamer and exhibit fascinating quaternary structural flexibility. These results suggest that optimal substrate channeling is achieved when a cyclase domain associates with the side of the PT octamer, regardless of whether the two domains are covalently linked and regardless of whether this interaction is transient or locked in place.