Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces. It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the E. coli enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the Francisella enzyme at 99 nM. Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin.
Isopentenyl pyrophosphate is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway and in the non-mevalonate MEP pathway of isoprenoid precursor biosynthesis. Isoprenoid precursors such as IPP, and its isomer DMAPP, are used by organisms in the biosynthesis of terpenes and terpenoids.
(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis. The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The currently preferred name for this pathway is the MEP pathway, since MEP is the first committed metabolite on the route to IPP.
2-C-Methyl-D-erythritol 4-phosphate (MEP) is an intermediate on the MEP pathway of isoprenoid precursor biosynthesis. It is the first committed metabolite on that pathway on the route to IPP and DMAPP.
1-Deoxy-d-xylulose 5-phosphate is an intermediate in the non-mevalonate pathway.
Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically more recently in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today: topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.
In enzymology, a 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (HMB-PP synthase, IspG, EC 1.17.7.1) is an enzyme that catalyzes the chemical reaction
2-C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase is a zinc-dependent enzyme and a member of the YgbB N terminal protein domain, which participates in the MEP pathway of isoprenoid precursor biosynthesis. It catalyzes the following reaction:
In enzymology, a 1-deoxy-d-xylulose-5-phosphate synthase (EC 2.2.1.7) is an enzyme in the non-mevalonate pathway that catalyzes the chemical reaction
In enzymology, a pyridoxine 5'-phosphate synthase (EC 2.6.99.2) is an enzyme that catalyzes the chemical reaction
In enzymology, a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase is an enzyme that catalyzes the chemical reaction:
In enzymology, a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase is an enzyme that catalyzes the chemical reaction
2-C-Methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) is an intermediate in the MEP pathway (non-mevalonate) of isoprenoid precursor biosynthesis. MEcPP is produced by MEcPP synthase (IspF) and is a substrate for HMB-PP synthase (IspG).
4-Diphosphocytidyl-2-C-methylerythritol is an intermediate in the MEP pathway of isoprenoid precursor biosynthesis. It is produced by the enzyme 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) and is a substrate for CDP-ME kinase (IspE).
4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate is an intermediate in the MEP pathway of isoprenoid precursor biosynthesis.
4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (EC 1.17.1.2, isopentenyl-diphosphate:NADP+ oxidoreductase, LytB, (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase, HMBPP reductase, IspH, LytB/IspH) is an enzyme in the non-mevalonate pathway. It acts upon (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (or "HMB-PP").
Withaferin A is a steroidal lactone, derived from Acnistus arborescens, Withania somnifera and other members of family Solanaceae. It is the first member of the withanolide class of ergostane type product to be discovered.
In molecular biology, YgbB is a protein domain. This entry makes reference to a number of proteins from eukaryotes and prokaryotes which share this common N-terminal signature and appear to be involved in terpenoid biosynthesis. The YgbB protein is a putative enzyme thought to aid terpenoid and isoprenoid biosynthesis, a vital chemical in all living organisms. This protein domain is part of an enzyme which catalyses a reaction in a complex pathway.
Michel Rohmer, born on 31 January 1948, is a French chemist specialising in the chemistry of micro-organisms. He has particularly studied isoprenoids.
