Communesin B Explained

Communesin B is a cytotoxic chemical compound isolated from Penicillium strains found on the marine alga Ulva intestinalis.[1] [2] It exhibits cytotoxicity in vitro against human lung carcinoma, prostate carcinoma, colorectal carcinoma, cervical adenocarcinoma, and breast adenocarcinoma cell lines.[3]

Biosynthesis

Communesin B is a dimeric indole alkaloid with a hexadienoyl moiety originating from polyketide synthesis. Biosynthesis starts with two L-tryptophan molecules processed by different pathways. The first pathway involves a decarboxylation step catalyzed by CnsB to produce tryptamine. The second pathway starts the synthesis of 4-L-dimethylallyl tryptophan by CnsF followed by further processing of CnsA and CnsD to form aurantioclavine. These two indole-containing fragments are combined through a radical oxidative coupling by CnsC, a cytochrome P450 enzyme, to form the core scaffold of communesin alkaloids.[4] CnsE transfers a methyl group to the indole nitrogen, and CnsJ creates an epoxide ring on the dimethylallyl substituent off the ring structure to form communesin I.[5] Separately, CnsI synthesizes a hexadienoyl group using acetyl-CoA as a starting material and extending it with two malonyl-CoA units. Then, CnsK performs N-acylation with the CnsI-synthesized hexadienoyl chain to form communesin B.

Notes and References

  1. Crawley SL, Funk RL . A synthetic approach to nomofungin/communesin B . Organic Letters . 5 . 18 . 3169–3171 . September 2003 . 12943379 . 10.1021/ol034407v .
  2. Nicoletti R, Trincone A . Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin . Marine Drugs . 14 . 2 . 37 . February 2016 . 26901206 . 4771990 . 10.3390/md14020037 . free .
  3. Pompeo . Matthew M. . Cheah . Jaime H. . Movassaghi . Mohammad . 2019-09-11 . Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives . Journal of the American Chemical Society . en . 141 . 36 . 14411–14420 . 10.1021/jacs.9b07397 . 0002-7863 . 6743222 . 31422662.
  4. Pompeo MM, Cheah JH, Movassaghi M . Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives . Journal of the American Chemical Society . 141 . 36 . 14411–14420 . September 2019 . 31422662 . 6743222 . 10.1021/jacs.9b07397 .
  5. Lin HC, Chiou G, Chooi YH, McMahon TC, Xu W, Garg NK, Tang Y . Elucidation of the concise biosynthetic pathway of the communesin indole alkaloids . Angewandte Chemie . 54 . 10 . 3004–3007 . March 2015 . 25571861 . 4409825 . 10.1002/anie.201411297 .