Cancer is a multifaceted global disease. Transformation of a normal to a malignant cell takes several steps, including somatic mutations, epigenetic alterations, metabolic reprogramming and loss of cell growth control. Recently, the mevalonate pathway has emerged as a crucial regulator of tumor biology and a potential therapeutic target. This pathway controls cholesterol production and posttranslational modifications of Rho-GTPases, both of which are linked to several key steps of tumor progression. Inhibitors of the mevalonate pathway induce pleiotropic antitumor-effects in several human malignancies, identifying the pathway as an attractive candidate for novel therapies. In this review, we will provide an overview about the role and regulation of the mevalonate pathway in certain aspects of cancer initiation and progression and its potential for therapeutic intervention in oncology.
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http://dx.doi.org/10.1016/j.bbcan.2020.188351 | DOI Listing |
J Agric Food Chem
January 2025
State Key Laboratory of Synthetic Biology, School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, China.
Ursolic acid, a plant-derived pentacyclic triterpenoid with anti-inflammatory, antioxidant, and other bioactive properties, holds significant potential for use in nutritional supplements and drug development. However, its extraction from medicinal plants is inefficient due to low yield and dependence on seasonality and geography. Herein, we use modular metabolic engineering to enhance ursolic acid production in by dividing the biosynthetic pathway into five modules.
View Article and Find Full Text PDFMetab Eng
January 2025
Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA, USA. Electronic address:
Prenol and isoprenol are promising advanced biofuels and serve as biosynthetic precursors for pharmaceuticals, fragrances, and other industrially relevant compounds. Despite engineering improvements that circumvent intermediate cytotoxicity and lower energy barriers, achieving high titer 'mevalonate (MVA)-derived' prenol has remained elusive. Difficulty in selective prenol production stems from the necessary isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP) as well as the intrinsic toxicity of these diphosphate precursors.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
State Key Laboratory of Tropical Crop Breeding, Sanya Institute, Rubber Research Institute, Chinese Academy of Tropical Agricultural Sciences, Sanya 572025, China.
The biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are essential for sesquiterpenes and triterpenes, respectively, is primarily governed by the mevalonate pathway, wherein () plays a pivotal role. This study identified eight members of the FPS gene family in , designated -, through bioinformatics analysis, revealing their distribution across several chromosomes and a notable tandem gene cluster. The genes exhibited strong hydrophilic properties and key functional motifs crucial for enzyme activity.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
State Key Laboratory of Tree Genetics and Breeding, Nanjing Forestry University, Nanjing 210037, China.
Terpenoids, abundant and structurally diverse secondary metabolites in plants, especially in conifer species, play crucial roles in the plant defense mechanism and plant growth and development. In , terpenoids' biosynthesis relies on both the mevalonate (MVA) pathway and the 2-methyl-D-erythritol-4-phosphate (MEP) pathway, with 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase (HDS) catalyzing the sixth step of the MEP pathway. In this study, we cloned and conducted bioinformatics analysis of the gene from .
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Ph.D. Program in Medical Neuroscience, Taipei Medical University and National Health Research Institutes, Taipei 11031, Taiwan; TMU Research Center for Drug Discovery, Taipei Medical University, Taipei 11031, Taiwan; International Master Program in Medical Neuroscience, Taipei Medical University, New Taipei City 23564, Taiwan; TMU Research Center of Neuroscience, Taipei Medical University, Taipei 11031, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80780, Taiwan. Electronic address:
Traumatic brain injury (TBI) constitutes a significant burden on global healthcare systems, especially affecting younger populations, where it is a leading cause of disability and mortality. Current treatments for TBI mainly focus on preventing further brain damage and controlling symptoms. However, despite these approaches, several clinical needs remain unmet.
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