Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Two-step pathway for isoprenoid synthesis.

ABSTRACT: Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.

SUBMITTER: Chatzivasileiou AO

PROVIDER: S-EPMC6329939 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The isoprenoid alcohol pathway, a synthetic route for isoprenoid biosynthesis.

Project description:The more than 50,000 isoprenoids found in nature are all derived from the 5-carbon diphosphates isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Natively, IPP and DMAPP are generated by the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, which have been engineered to produce compounds with numerous applications. However, as these pathways are inherently constrained by carbon, energy inefficiencies, and their roles in native metabolism, engineering for isoprenoid biosynthesis at high flux, titer, and yield remains a challenge. To overcome these limitations, here we develop an alternative synthetic pathway termed the isoprenoid alcohol (IPA) pathway that centers around the synthesis and subsequent phosphorylation of IPAs. We first established a lower IPA pathway for the conversion of IPAs to isoprenoid pyrophosphate intermediates that enabled the production of greater than 2 g/L geraniol from prenol as well as limonene, farnesol, diaponeurosporene, and lycopene. We then designed upper IPA pathways for the generation of (iso)prenol from central carbon metabolites with the development of a route to prenol enabling its synthesis at more than 2 g/L. Using prenol as the linking intermediate further facilitated an integrated IPA pathway that resulted in the production of nearly 0.6 g/L total monoterpenoids from glycerol as the sole carbon source. The IPA pathway provides an alternative route to isoprenoids that is more energy efficient than native pathways and can serve as a platform for targeting a repertoire of isoprenoid compounds with application as high-value pharmaceuticals, commodity chemicals, and fuels.

| S-EPMC6600936 | biostudies-literature

The two-step mechanochemical synthesis of porphyrins.

Project description:Porphyrin synthesis under solvent-free conditions represents the "greening" of a traditional synthesis that normally requires large amounts of organic solvent, and has hindered the industrial-scale synthesis of this useful class of molecules. We have found that the four-fold acid-catalysed condensation of aldehyde and pyrrole to yield a tetra-substituted porphyrin is possible through mechanochemical techniques, without a solvent present. This represents one of the still-rare examples of carbon-carbon bond formation by mechanochemistry. Specifically, upon grinding equimolar amounts of pyrrole and benzaldehyde in the presence of an acid catalyst, cyclization takes place to give reduced porphyrin precursors (reversible), which upon oxidation form tetraphenylporphyrin (TPP). The approach has been found to be suitable for the synthesis of a variety of meso-tetrasubstituted porphyrins. Oxidation can occur either by using an oxidizing agent in solution, to give yields comparable to those published for traditional methods of porphyrin synthesis, or through mechanochemical means resulting in a two-step mechanochemical synthesis to give slightly lower yields that are still being optimized. We are also working on "green" methods of porphyrin isolation, including entrainment sublimation, which would hopefully further reduce the need for large amounts of organic solvent. These results hold promise for the development of mechanochemical synthetic protocols for porphyrins and related classes of compounds.

| S-EPMC4238103 | biostudies-literature

Concise two-step chemical synthesis of molnupiravir.

Project description:A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

| S-EPMC9585438 | biostudies-literature

One-pot, two-step cascade synthesis of quinazolinotriazolobenzodiazepines.

Project description:An operationally simple, one-pot, two-step cascade method has been developed to afford quinazolino[1,2,3]triazolo[1,4]benzodiazepines. This unique, atom-economical transformation engages five reactive centers (amide, aniline, carbonyl, azide, and alkyne) and employs environmentally benign iodine as a catalyst. The method proceeds via sequential quinazolinone-forming condensation and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions. Substrate scope, multicomponent examples, and mechanistic insights are discussed.

| S-EPMC3486955 | biostudies-literature

Two-Step Macrocycle Synthesis by Classical Ugi Reaction.

Project description:The direct nonpeptidic macrocycle synthesis of α-isocyano-ω-amines via the classical Ugi four-component reaction (U-4CR) is introduced. Herein an efficient and flexible two-step procedure to complex macrocycles is reported. In the first step, the reaction between unprotected diamines and isocyanocarboxylic acids gives high diversity of unprecedented building blocks in high yield. In the next step, the α-isocyano-ω-amines undergo a U-4CR with high diversity of aldehydes and carboxylic acids in a one-pot procedure. This synthetic approach is short and efficient and leads to a wide range of macrocycles with different ring sizes.

| S-EPMC5799868 | biostudies-literature

Two-Step Synthesis of Complex Artificial Macrocyclic Compounds.

Project description:The design and synthesis of head-to-tail linked artificial macrocycles using the Ugi-reaction has been developed. This synthetic approach of just two steps is unprecedented, short, efficient and works over a wide range of medium (8-11) and macrocyclic (≥12) loop sizes. The substrate scope and functional group tolerance is exceptional. Using this approach, we have synthesized 39 novel macrocycles by two or even one single synthetic operation. The properties of our macrocycles are discussed with respect to their potential to bind to biological targets that are not druggable by conventional, drug-like compounds. As an application of these artificial macrocycles we highlight potent p53-MDM2 antagonism.

| S-EPMC5660312 | biostudies-literature

The bacterium Thermus thermophilus, like hyperthermophilic archaea, uses a two-step pathway for the synthesis of mannosylglycerate.

Project description:The biosynthetic pathway for the synthesis of the compatible solute alpha-mannosylglycerate (MG) in the thermophilic bacterium Thermus thermophilus HB27 was identified based on the activities of recombinant mannosyl-3-phosphoglycerate synthase (MPGS) (EC 2.4.1.217) and mannosyl-3-phosphoglycerate phosphatase (MPGP) (EC 3.1.3.70). The sequences of homologous genes from the archaeon Pyrococcus horikoshii were used to identify MPGS and MPGP genes in T. thermophilus HB27 genome. Both genes were separately cloned and overexpressed in Escherichia coli, yielding 3 to 4 mg of pure recombinant protein per liter of culture. The molecular masses were 43.6 and 28.1 kDa for MPGS and MPGP, respectively. The recombinant MPGS catalyzed the synthesis of alpha-mannosyl-3-phosphoglycerate (MPG) from GDP-mannose and D-3-phosphoglycerate, while the recombinant MPGP catalyzed the dephosphorylation of MPG to MG. The recombinant MPGS had optimal activity at 80 to 90 degrees C and a pH optimum near 7.0; MPGP had maximal activity between 90 and 95 degrees C and at pH 6.0. The activities of both enzymes were strictly dependent on divalent cations; Mn(2+) was most effective for MPGS, while Mn(2+), Co(2+), Mg(2+), and to a lesser extent Ni(2+) activated MPGP. The organization of MG biosynthetic genes in T. thermophilus HB27 is different from the P. horikoshii operon-like structure, since the genes involved in the conversion of fructose-6-phosphate to GDP-mannose are not found immediately downstream of the contiguous MPGS and MPGP genes. The biosynthesis of MG in the thermophilic bacterium T. thermophilus HB27, proceeding through a phosphorylated intermediate, is similar to the system found in hyperthermophilic archaea.

| S-EPMC161470 | biostudies-literature

Two-step synthesis of the immunogenic bacterial glycolipid BbGL1.

Project description:Chemical synthesis of a bacterial glycolipid BbGL1 is reported in two steps starting from per-O-TMS D-galactose. The key features are glycosyl iodide mediated beta-stereoselective glycosylation in the absence of neighboring group participation and regioselective acylation.

| S-EPMC4492534 | biostudies-literature

Two-step enzymatic synthesis of 6-deoxy-L-psicose.

Project description:Rare sugars offer a plethora of applications in the pharmaceutical, medicinal, and industries, as well as in synthetic chemistry. However, studies of rare sugars have been hampered by their relative scarcity. In this work, we describe a two-step strategy to efficiently and conveniently prepare 6-deoxy-L-psicose from L-rhamnose. In the first reaction step, the isomerization of L-rhamnose (6-deoxy-L-mannose) to L-rhamnulose (6-deoxy-L-fructose) catalyzed by L-rhamnose isomerase (RhaI), and the epimerization of L-rhamnulose to 6-deoxy-L-psicose catalyzed by D-tagatose 3-epimerase (DTE) were coupled with selective phosphorylation reaction by fructose kinase from human (HK), which selectively phosphorylate 6-deoxy-L-psicose at C-1 position. 6-deoxy-L-psicose 1-phosphate was purified by a silver nitrate precipitation method. In the second step, the phosphate group of the 6-deoxy-L-sorbose 1-phosphate was hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-L-psicose in 81% yield with respect to L-rhamnose. This method allows that the 6-deoxy-L-psicose to be obtained from readily available starting materials with high purity and without having to undergo isomer separation.

| S-EPMC4990140 | biostudies-literature

Two-step Synthesis of Solasodine Pivalate from Diosgenin Pivalate.

Project description:A two-step synthesis of solasodine pivalate from diosgenin pivalate is described. The key transformation involves the reaction of diosgenin pivalate with benzyl carbamate (CbzNH?) promoted by TMSOTf. During the reaction the F-ring of the spiroketal moiety opens up with a simultaneous introduction of a Cbz-protected amino group in position 26. A one-pot deprotection of 26-amine with AcBr/BuOH followed by the N-cyclization affords solasodine pivalate in 45% overall yield.

| S-EPMC6471385 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data