Non-Heme Iron Enzymes Catalyze Heterobicyclic and Spirocyclic Isoquinolone Core Formation in Piperazine Alkaloid Biosynthesis.

Autor: Pham MT; Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Department of Chemistry, National Tsing Hua University, Hsinchu, 300, Taiwan R.O.C., Yang FL; Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C., Liu IC; Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C., Liang PH; Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C., Lin HC; Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 May 13; Vol. 63 (20), pp. e202401324. Date of Electronic Publication: 2024 Apr 09.
DOI: 10.1002/anie.202401324
Abstrakt: We report the discovery and biosynthesis of new piperazine alkaloids-arizonamides, and their derived compounds-arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non-heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3-alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.
(© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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