Unravelling the mystery of tropolones biosynthesis

Researchers from the University of Bristol, United Kingdom, and Future University in Egypt, have solved the 70-year-old mystery of how a class of non-benzenoid aromatic compounds called tropolones is synthesized in fungi. Publishing their findings in the Proceeding of the National Academy of Sciences (PNAS), the team used a combination of genetic and chemical techniques to unravel tropolone's biosynthetic pathway.

They blocked the synthetic pathway of the production in fungi at various steps and investigated the results. This allowed them to identify the specific genes responsible for the process, and demonstrated on a molecular scale how the unique, seven-membered carbon ring structure of tropolones is produced.

Using the fungus Talaromyces stipitatus, which produces the tropolone stipitatic acid, the team searched for an enzyme complex in the fungus' genome that is a known precursor for tropolone biosynthesis.

They found three oxidative enzymes; TropB, TropC and TropD, were key genes in the biosynthetic process leading to the production of tropolone.

This unravels a longstanding chemical mystery and coul d have medical benefits. Some tropolones are known to have anti-bacterial properties and may have potential for use in antimalarial treatments. Understanding their biosynthetic pathway may lead to the discovery of new drugs. The researchers are now planning to engineer fungi to produce large concentrations of these compounds.

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