6-MSA, a secondary metabolite distribution hub with multiple fungal destinations

6-methylsalicylic acid (6-MSA) is a small, simple polyketide produced by a broad spectrum of fungal species. Since fungi obtained the ability to synthesize 6-MSA from bacteria through a horizontal gene transfer event, it has developed into a multipurpose metabolic hub from where numerous complex compounds are produced. The most relevant metabolite from a human perspective is the small lactone patulin as it is one of the most potent mycotoxins. Other important end products derived from 6-MSA include the small quinone epoxide terreic acid and the prenylated yanuthones. The most advanced modification of 6-MSA is observed in the aculin biosynthetic pathway, which is mediated by a non-ribosomal peptide synthase and a terpene cyclase. In this short review, we summarize for the first time all the possible pathways that takes their onset from 6-MSA and provide a synopsis of the responsible gene clusters and derive the resulting biosynthetic pathways.

Automated summary

6-methylsalicylic acid (6-MSA) is a small polyketide produced by fungi through horizontal gene transfer, serving as a metabolic hub for the production of various complex compounds. The most significant metabolite derived from 6-MSA is the mycotoxin patulin. Other important products include terreic acid and yanuthones. The aculin biosynthetic pathway demonstrates the most advanced modification of 6-MSA, involving non-ribosomal peptide synthase and terpene cyclase. This review summarizes the pathways originating from 6-MSA, gene clusters involved, and resulting biosynthetic pathways.