Mycophenolic acid (MPA), discovered in 1893, was the first natural antibiotic to be isolated and crystallized in human history.

Today, this fungal metabolite has been developed into multiple first-line immunosuppressive drugs to control immunologic rejection during organ transplantation and treat various autoimmune diseases.

However, the biogenesis of such an old and important molecule was an unsolved mystery for more than a century.

Recently, scientists from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences cracked this intriguing black box by fully elucidating the biosynthetic pathway of MPA.

The results were published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The researchers revealed that MPA biogenesis requires very unique cooperation between biosynthetic enzymes and β-oxidation catabolic machinery.

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