Scientists at the Universities of Bristol and Newcastle have uncovered the secret of the ‘Mona Lisa of chemical reactions’ – in a bacterium that lives at the bottom of the Pacific Ocean. It is hoped the discovery could lead to the development of new antibiotics and other medical treatments.
The Diels-Alder reaction, discovered by Nobel Prize-wining chemists Otto Diels and Kurt Alder, is one of the most powerful chemical reactions known, and is used extensively by synthetic chemists to produce many important molecules, including antibiotics, anti-cancer drugs and agrochemicals.
However, there has been much debate and controversy about whether nature uses the reaction to produce its own useful molecules. If it does, the identity of the biological catalysts (enzymes) responsible for performing this reaction have remained a mystery until now.
Some candidate natural ‘Diels-Alderases’ have been identified, but these have either been shown not to perform the reaction, or the evidence that they catalyse a Diels-Alder reaction is ambiguous.
Now, researchers at BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre at the University of Bristol and the School of Biology at Newcastle University have conclusively shown that a true ‘Diels-Alderase’ (Diels-Alder enzyme) exists. They have also established in atomic detail how it catalyses the reaction.
Dr Paul Race, from BrisSynBio, said: “We found the enzyme, called AbyU, in a bacterium called Verrucosispora maris (V. maris), which lives on the Pacific seabed. V. maris uses the AbyU enzyme to biosynthesise a molecule called abyssomicin C, which has potent antibiotic properties.”
To establish the details of how the AbyU enzyme catalyses the Diels-Alder reaction, the team first had to solve the atomic structure of AbyU, and then simulate the enzyme reaction using quantum mechanics methods.
Dr Race said: “Once we had figured out how AbyU was able to make natural antibiotic, we were able to show that it could also perform the Diels-Alder reaction on other molecules that are difficult to transform using synthetic chemistry.”
The team are now investigating ways of using the enzyme to make molecules similar to abyssomisin C, in the hope that antibiotics are found that are even more effective than the natural molecule.
Dr Race said: “What is particularly exciting about our work is that not only have we resolved the riddle of the natural Diels-Alderase, but we have also shown that the enzyme can perform Diels-Alder reactions that are challenging to perform using synthetic chemistry. The work opens up a raft of possibilities for making new useful molecules that could, for example, form the basis of new medicines, materials, or commodity chemicals.”
Co-author Dr Marc van der Kamp, from BrisSynBio, said: “The work has been a great example of interdisciplinary collaboration, using techniques from biology, chemistry, physics and mathematics. As the computational chemist in the team, I am particularly pleased how a broad range of computer simulation techniques has been integral to the work, revealing details about the dynamical behaviour of the enzyme, how the substrate interacts with it, and how this interaction results in generating the Diels-Alder product.”
Dr Jem Stach, from Newcastle University, was also a co-author of the paper. He said: “Nature, not only in the compounds it produces, but also the means by which it does so, is the best chemist. This has never been clearer to me than it was during this collaboration between biologists and chemists. Starting with genome gazing, and ending with new chemistry, on a journey that took in structural biology, synthetic chemistry and computational chemistry, was utterly rewarding, educational and fascinating.”
Learn more: An enzyme enigma discovered in the abyss
The Latest on: Diels-Alder reactions
via Google News
The Latest on: Diels-Alder reactions
- Diels-Alder Reaction Gains Nobel Prizeon November 17, 2019 at 12:00 am
- A very large number of Diels-Alder reactions are recorded in the chemical literature, many of...on September 30, 2019 at 4:27 am
The Diels Alder reaction occurs in a single step. The breaking of bonds and formation of bonds occurs at the same time. The diene and dienophile reacts to form adduct. The corresponding reaction is ...
- Fungal-Derived Drugs Have Unexpected “Reaction”on September 24, 2019 at 5:10 am
The final step in the assembly process is a reaction that is nearly unprecedented in nature: the Diels-Alder reaction. “This reaction is one of the fundamentals of synthetic organic chemistry, going ...
- Draw the products of the following Diels-Alder reactions. (Indicate the required stereochemistry...on September 15, 2019 at 5:10 pm
Stereochemistry is not shown on double bond. The reaction is shown below. Diels-alder product of (a) Therefore, the product of (a) is (3R,6S)-diethyl ...
- Divergent synthesis of chiral cyclic azides via asymmetric cycloaddition reactions of vinyl azideson July 18, 2019 at 2:10 am
α-Aryl substituted vinyl azides react with unsaturated keto esters through an inverse-electron-demand hetero-Diels-Alder reaction to afford chiral azido dihydropyrans with excellent ...
- Electric field–induced selective catalysis of single-molecule reactionon June 21, 2019 at 7:10 pm
1 State Key Laboratory of Physical Chemistry of Solid Surfaces, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), National Engineering Laboratory for Green Chemical ...
- A multi-substrate screening approach for the identification of a broadly applicable Diels–Alder catalyston February 15, 2019 at 2:20 am
Using this multi-substrate screening approach, we have identified an efficient and stereoselective imidodiphosphorimidate organocatalyst for scalable Diels–Alder reactions of cyclopentadiene with ...
- Artificial enzymes perform reactions on living cellson July 26, 2018 at 1:42 pm
Wadih Ghattas, Jean-Pierre Mahy and their colleagues set their sights on engineering an artificial enzyme that could catalyze a useful reaction, called the Diels-Alder reaction, right on the surfaces ...
- RUDN chemists have completely changed the direction of Diels-Alder reactionon June 27, 2018 at 7:55 am
The Diels-Alder reaction is widely used in organic synthesis. Chemists appreciate its simplicity, reliability, and the ability to influence its course and change the conditions of the process. Several ...
- Catalyst closes a gap in hetero Diels-Alder reactionon September 29, 2017 at 12:58 pm
Chiral IDPi catalysts expand the scope of hetero Diels-Alder reactions beyond electronically biased partners. The Diels-Alder reaction is a classic transformation that typically marries a diene (with ...
via Bing News