enzyme GGPS expression in crop plants may yield desirable agronomic traits, including enhanced growth of shoots and roots, early flowering, greater numbers of seed pods and/or higher seed yield with potential applications for fast production of plant biomass that provides commercially valuable biomaterials or bioenergy
reconstruction of the isoprenoid pathway in Escherichia coli. To engineer a host that has the capability to supply geranylgeranyl diphosphate, a common precursor of isoprenoids, isopentenyl diphosphate isomerase (encoded by idi) from Escherichia coli and geranylgeranyl diphosphate synthase (encoded by gps) from Archaeoglobus fulgidus are cloned and overexpressed. The latter is shown to be a multifunctional enzyme converting dimethylallyl diphosphate to geranylgeranyl diphosphate. These two genes and the gene cluster (crtBIYZW) of the marine bacterium Agrobacterium aurantiacum are introduced into Escherichia coli to produce astaxanthin, an orange pigment and antioxidant. The metabolically engineered strain produces astaxanthin at a very high rate
overexpression of geranylgeranyl diphosphate synthase correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating epithelial-mesenchymal transition
engineering of Yarrowia lipolytica for de novo production of the food and feed additive astaxanthin by fermentation. The astaxanthin-producing Yarrowia lipolytica shows great promise for employment in biological astaxanthin production. The genes for beta-carotene biosynthesis: bi-functional phytoene synthase/lycopene cyclase (crtYB) and phytoene desaturase (crtI) from Xanthophyllomyces dendrorhousa are introduced. The activities of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG1) and geranylgeranyl diphosphate synthase (GGS1/crtE) in the best producing strain are optimized. Downregulation of the competing squalene synthase SQS1 increases the beta-carotene titer. Then a beta-carotene ketolase (crtW) from Paracoccus sp. N81106 and hydroxylase (crtZ) from Pantoea ananatis are introduced to convert beta-carotene into astaxanthin. The constructed strain accumulates 10.4 mg/l of astaxanthin but also accumulates astaxanthin biosynthesis intermediates, 5.7 mg/l canthaxanthin, and 35.3 mg/l echinenone. The copy numbers of crtZ and crtW are optimized to obtain 3.5 mg/g dry cell weight (54.6 mg/l) of astaxanthin in a microtiter plate cultivation
validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism
the enzyme possibly represents an attractive drug target for the development of selective inhibitors aiming the erythrocytic stages of Plasmodium falciparum and development of more potent bisphosphonate-based inhibitors selectivity targeting this key point of the plasmodial isoprenoid metabolism
the enzyme possibly represents an attractive drug target for the development of selective inhibitors aiming the erythrocytic stages of Plasmodium falciparum and development of more potent bisphosphonate-based inhibitors selectivity targeting this key point of the plasmodial isoprenoid metabolism
the enzyme in Xanthophyllomyces is used for production of astaxanthin, i.e. 3,3'-hydroxy-4,4'-diketo-beta-carotene, which is an industrially important carotenoid used for feeding salmon or trout in farming
the enzyme in Xanthophyllomyces is used for production of astaxanthin, i.e. 3,3'-hydroxy-4,4'-diketo-beta-carotene, which is an industrially important carotenoid used for feeding salmon or trout in farming
this enzyme is an attractive target for drug development, because the order of inhibition of the enzyme by a number of bisphosphonates is the same as that for inhibition of parasite growth. This enzyme as a valid target for the chemotherapy of toxoplasmosis
women with 2 deletion alleles of GGPS1 -8188A ins/del (rs3840452) have significantly higher femoral neck bone marrow densitiy at baseline compared with those with one or no deletion allele. The response rate of women with 2 deletion alleles of GGPS1 -8188A ins/del (28.6%) is significantly lower than the rate of women with one or no deletion allele. Women with 2 deletion alleles of GGPS1 -8188A ins/del have 7fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188. Other polymorphisms in or GGPS1 are not associated with lumbar spine bone marrow density or femoral neck bon marrow density
validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism
enzyme expression is significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of geranylgeranyl diphosphate synthase is correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients
geranylgeranyl diphosphate biosynthesized by Ginkgo biloba geranylgeranyl diphosphate synthase is an importent key precu´rsor for ginkgolides with pharmaceutical interest
geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma
the enzyme is an antimalarial drug target. Current bisphosphonate drugs that inhibit farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for the bifunctional farnesyl/geranylgeranyl diphosphate synthase in Plasmodium falciparum. The non-bisphosphonate compound, MMV019313, which is highly selective for the bifunctional farnesyl/geranylgeranyl diphosphate synthase shows no activity against human farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes
the enzyme is an antimalarial drug target. Current bisphosphonate drugs that inhibit farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for the bifunctional farnesyl/geranylgeranyl diphosphate synthase in Plasmodium falciparum. The non-bisphosphonate compound, MMV019313, which is highly selective for the bifunctional farnesyl/geranylgeranyl diphosphate synthase shows no activity against human farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes
the enzyme in Xanthophyllomyces is used for production of astaxanthin, i.e. 3,3'-hydroxy-4,4'-diketo-beta-carotene, which is an industrially important carotenoid used for feeding salmon or trout in farming
to engineer a host that has the capability to supply geranylgeranyl diphosphate, a common precursor of isoprenoids, isopentenyl diphosphate isomerase (encoded by idi) from Escherichia coli and geranylgeranyl diphosphate synthase (encoded by gps) from Archaeoglobus fulgidus are cloned and overexpressed. The latter is shown to be a multifunctional enzyme converting dimethylallyl diphosphate to geranylgeranyl diphosphate. These two genes and the gene cluster (crtBIYZW) of the marine bacterium Agrobacterium aurantiacum are introduced into Escherichia coli to produce astaxanthin, an orange pigment and antioxidant. The metabolically engineered strain produces astaxanthin at a very high rate
the enzyme in Xanthophyllomyces is used for production of astaxanthin, i.e. 3,3'-hydroxy-4,4'-diketo-beta-carotene, which is an industrially important carotenoid used for feeding salmon or trout in farming