Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• clans, families, and subfamilies. The broadest hierarchy level is represented by clans, which comprise one or multiple families. An example CYP name is CYP51G1; here, “CYP51” designates the family, “G” refers to the subfamily within the CYP51 family, and “1” represents the isoform of CYPs in this

• other families of the CYP85 clan such as CYP87, CYP85, or CYP90 contain mostly triterpene-modifying CYPs to date. The small clans CYP51 and CYP710 are other important examples of groups with a high preference for triterpenoid substrates. The highly diverse CYP71 clan, in contrast, only contains a few

• four CYPs could produce stigmasterol from β-sitosterol (2) in enzyme assays performed in vitro. However, Arabidopsis CYP710A2 showed substrate flexibility towards campesterol (1) epimers and could also produce brassicasterol from 24-epicampesterol in vitro. Enzymes of the CYP51G subfamily (CYP51 clan

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• of this new class of inhibitors. Keywords: activity-based probes; Chagas’ disease; cruzain; CYP51; 14-α-demethylase; hybrid drugs; Trypanosoma cruzi; Introduction The kinetoplastid protozoan Trypanosoma cruzi is the causative agent of Chagas’ disease, a leading cause of heart failure in endemic

• investigated are cruzain [7][8][9][10], the major cysteine protease active in the parasite, and T. cruzi CYP51 (TcCYP51), a 14-α-demethylase enzyme of the cytochrome P450 family required for ergosterol biosynthesis [11][12][13][14]. TcCYP51 is analogous to the fungal enzyme targeted by the azole class of

• performed concurrently with other CYP51 inhibitors described recently [33] and, thus, the spectra for the controls shown above are reproduced from the earlier report. Spectra of lipid extracts from parasites treated with 3, 6, 7, and 8 are provided in Supporting Information File 1. Uninfected host cell