How tropolones synthesized in fungi: 70-year-old chemical mystery solved

Apr 16, 2012

Chemists and biologists from the University of Bristol have finally cracked one of the longest standing chemical mysteries. In a paper published today in the Proceedings of the National Academy of Sciences, the team demonstrate exactly how an unusual class of compounds known as tropolones are synthesized in fungi.

In 1942, an 'unidentifiable' aromatic compound known as stipitatic acid was first isolated from fungi. By 1945 the structure was solved but it was so unique that it caused a revolution in the understanding of organic chemistry.

Stipitatic acid is very unusual as it displays similar aromatic properties to the six-membered rings in benzene-based compounds, but is a seven-membered carbon ring known as a tropolone. New developed to understand tropolones now underpin our understanding of structure and bonding in .

However it remained a mystery as to how fungi are able to synthesise such a product under biological conditions – until now.

Using a combination of genetic and chemical methods, Dr Andy Bailey and Professor Russell Cox and colleagues were able to identify the genes responsible for this process, blocking the synthetic pathway at different steps and thus demonstrating how, on a molecular scale, the tropolone structure is produced. This is the core of a number of fungal compounds including stipitatic acid, the xenovulenes which are antidepressants and the antimalarial compound puberulic acid.

Knowledge of tropolone biosynthetic pathway is in itself very interesting to , but it may also lead to the discovery of new drugs.

Professor Russell Cox of Bristol's School of Chemistry, who led the project, said: "Members of this class of compound are well known as having antibacterial properties and some have promise as antimalarial treatments – we now plan to engineer to produce these new compounds."

It is hoped that identification of the enzymes responsible for tropolone synthesis will help in generating a wider range of compounds for evaluation.

Explore further: Research team announces new class of compounds that appear to be effective against malaria

More information: 'The Genetic, Molecular and Biochemical Basis of Fungal Tropolone Biosynthesis' by Jack Davison, Ahmed al-Fahad, Menghao Cai, Zhongshu Song, Samar Yehia, Colin M. Lazarus, Andrew M. Bailey, Thomas J. Simpson and Russell J. Cox in Proceedings of the National Academy of Sciences (2012).

Related Stories

Probing the secrets of the ryegrasses

Jun 20, 2011

Loline alkaloids protect plants from attack by insects and have other interesting features that have yet to be studied in detail. Chemists from Ludwig-Maximilians-Universitaet in Munich, Germany, have developed a method for ...

New compound effectively treats fungal infections

Jun 22, 2007

A new mechanism to attack hard-to-treat fungal infections has been revealed by scientists from the biotech company Anacor Pharmaceuticals Inc., California, and the European Molecular Biology Laboratory (EMBL) outstation in ...

Recommended for you

Molecules that came in handy for first life on Earth

Nov 24, 2014

For the first time, chemists have successfully produced amino acid-like molecules that all have the same 'handedness', from simple building blocks and in a single test tube. Could this be how life started. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.