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Methyl erythritol phosphate (MEP) is the metabolite found in the MEP pathway for isoprenoid biosynthesis, which is known to be utilized by plants, algae, and bacteria. In this study, an unprecedented observation was found in the oleaginous yeast Yarrowia lipolytica, in which one of the chromatographic peaks was annotated as MEP when cultivated in the nitrogen limiting condition. This finding raised an interesting hypothesis of whether Y. lipolytica utilizes the MEP pathway for isoprenoid biosynthesis or not, because there is no report of yeast harboring the MEP pathway. Three independent approaches were used to investigate the existence of the MEP pathway in Y. lipolytica; the spiking of the authentic standard, the MEP pathway inhibitor, and the C labeling incorporation analysis. The study suggested that the mevalonate and MEP pathways co-exist in Y. lipolytica and the nitrogen limiting condition triggers the utilization of the MEP pathway in Y. lipolytica.
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http://dx.doi.org/10.1038/s41598-021-85170-0 | DOI Listing |
RSC Med Chem
August 2025
Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech 1040 Drillfield Drive Blacksburg VA 24061 USA.
Tetrahydro-β-carboline 1 (MMV008138) controls growth of asexual blood-stage by inhibiting IspD, an enzyme in the MEP pathway for synthesis of a critical metabolite, isopentenyl pyrophosphate (IPP). We have previously investigated the structure activity relationship (SAR) of three of its four rings (B, C, and D). In this report we investigate the SAR of the benzo- ( A-ring) of 1, with the goal of increasing its antimalarial potency and metabolic stability.
View Article and Find Full Text PDFPlant Cell Environ
August 2025
Division of Crop Production and Protection, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
Pelargonium graveolens, valued for its essential oil, is significantly influenced by its endosymbiotic associations impacting its physiology and phytochemistry, though the exact mechanisms driving this modulation remain largely unexplored. This study unveils that inoculating Pseudomonas oryzihabitans CB24 into P. graveolens significantly alters plant's lipid dynamics, leading to increased accumulation of chloroplast glycerolipids like monogalactosyldiacylglycerol (MGDG) and sulfolipids, sulfoquinovosyldiacylglycerol (SQDG).
View Article and Find Full Text PDFACS Nano
August 2025
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
Gram-negative bacteria are increasingly resistant to antibiotics, making the development of effective antimicrobial agents crucial in combating global health threats. In this context, IspH, a key enzyme in the methylerythritol phosphate (MEP) pathway essential for isoprenoid biosynthesis, represents a promising target to develop antibacterial agents for ablating Gram-negative bacteria. However, the anionic groups commonly present in IspH inhibitors hinder their ability to penetrate bacterial cells, preventing them from exhibiting biological activity.
View Article and Find Full Text PDFBioorg Chem
August 2025
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus Building E8.1, 66123 Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus Building E8.1, 66123 Saarbrücken, Germany; PharmaScienceHub, Campus Building E2.1,
Klebsiella pneumoniae is a critical-priority pathogen based on the 2024 WHO list and poses a significant threat to human health. The methylerythritol phosphate (MEP) pathway, crucial for isoprenoid biosynthesis in many pathogenic bacteria, including K. pneumoniae, represents a promising source of targets for antibacterial drug discovery.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Terpenoids are structurally complex natural products with broad agricultural and therapeutic value, yet their low natural abundance and oxidative tailoring requirements complicate scalable production. Conventional microbial hosts often fail to support cytochrome P450-mediated oxidative tailoring, limiting access to complex derivatives. Here, we developed two hosts as alternative chassis, leveraging their extensive biosynthetic capabilities and native oxidative enzyme repertoires.
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