Chaetoglobosin A Explained

Chaetoglobosin A is a fungal isolate with anticancer activity in vitro.[1] Derivatives of the compound include MBJ-0038, MBJ-0039, and MBJ-0040.[2]

Biosynthesis

Chaetoglobosin A biosynthesis begins with a product from hybrid PKS-NRPS encoded by the gene CHGG_01239, followed by multiple oxidations which form different intermediates depending on the order of functional groups oxidized. The PKS-NRPS product undergoes a diels alder, to form I (2) and is subsequently oxidized in different paths as shown in the scheme. Either the epoxide is created first to form IV (5), followed by di-hydroxylation to form 20-dihydrochaetoglobosin A (6), and a final oxidation of one hydroxyl to ketone to form chaetoglobosin A, or di-hydroxylation of (2) occurs first, forming cytoglobosin D (3), followed by one hydroxyl oxidation to form chaetoglobosin J (4), and lastly epoxidation to form chaetoglobosin A. Epoxidation of (3) can also occur prior to hydroxyl oxidation to form (6). [3]

Notes and References

  1. Tetrahedron Lett.. 14. 23. 1973. 2109–2112. Structures of chaetoglobosin A and B, cytotoxic metabolites of Chaetomium globosum. Sekita, S. . Yoshihara, K. . Kuwano, H. . 10.1016/S0040-4039(01)86820-9.
  2. 23881215 . New chaetoglobosin derivatives, MBJ-0038, MBJ-0039 and MBJ-0040, isolated from the fungus Chaetomium sp. f24230 . 2013 . Kawahara . T . Itoh . M . Izumikawa . M . Sakata . N . Tsuchida . T . Shin-Ya . K . 10.1038/ja.2013.75 . The Journal of Antibiotics . 66 . 12 . 727–30. 2926936 .
  3. Ishiuchi. Kan’ichiro. Nakazawa. Takehito. Yagishita. Fumitoshi. Mino. Takashi. Noguchi. Hiroshi. Hotta. Kinya. Watanabe. Kenji. Combinatorial Generation of Complexity by Redox Enzymes in the Chaetoglobosin A Biosynthesis. Journal of the American Chemical Society. en. 135. 19. 7371–7377. 10.1021/ja402828w. 23611317. 2013.