Elucidation of the Concise Biosynthetic Pathway of the Communesin Indole Alkaloids

Abstract

The communesins are a prominent class of indole alkaloids isolated from Penicillium species. Owing to their daunting structural framework and potential as pharmaceuticals, communesins have inspired numerous synthetic studies. However, the genetic and biochemical basis of communesin biosynthesis has remained unexplored. Herein, we report the identification and characterization of the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We confirmed that communesin is biosynthesized by the coupling of tryptamine and aurantioclavine, two building blocks derived from L‐tryptophan. The postmodification steps were mapped by targeted‐gene‐deletion experiments and the structural elucidation of intermediates and new analogues. Our studies set the stage for the biochemical characterization of communesin biosynthesis. This knowledge will aid our understanding of how nature generates remarkable structural complexity from simple precursors.

Synthesis of 3,4‐Fused Tricyclic Indoles Using 3‐Alkylidene Indolines as Versatile Precursors

“…The absolute configuration was determined to be R by the enantioselective total synthesis by Stoltz et al . (−)‐Aurantioclavine is a biosynthetic intermediate of communesins, complex polycyclic alkaloids with various bioactivities . (−)‐Aurantioclavine is therefore an attractive target for synthetic organic and medicinal chemists.…”

Derivation of the multiply‐branched ergot alkaloid pathway of fungi

“…Penicillium camemberti accumulates N‐methyl‐DMAT (requiring only the genes dmaW and easF ) under certain culture conditions but not in cheese (Fabian et al, 2018). Lin et al (2015) showed that genes cnsF (a homologue of dmaW ), cnsA (a homologue of easE ) and cnsD (a homologue of easC ) from Penicillium expansum can synthesize aurantioclavine. These three genes represent the enzyme complement required for chanoclavine‐I biosynthesis minus the N‐methyl transferase encoded by easF .…”

“…These three genes represent the enzyme complement required for chanoclavine‐I biosynthesis minus the N‐methyl transferase encoded by easF . Aurantioclavine may then be coupled with tryptamine derivatives to produce the complex family of communesins (Lin et al, 2015).…”