Details

Autor(en) / Beteiligte

• Yang, Jiali
• Mori, Takahiro
• Wei, Xingxing
• Matsuda, Yudai
• Abe, Ikuro

Titel

Structural Basis for Isomerization Reactions in Fungal Tetrahydroxanthone Biosynthesis and Diversification

Ist Teil von

• Angewandte Chemie International Edition, 2021-08, Vol.60 (35), p.19458-19465

Auflage

International ed. in English

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The novel isomerase NsrQ, from Aspergillus novofumigatus, is a key enzyme in the biosynthesis of fungal tetrahydroxanthones and is responsible for dearomatizing cyclization to provide a tetrahydroxanthone scaffold. NsrQ catalyzes a two‐step isomerization reaction, involving the isomerization of allylic alcohol and subsequent inversion of configuration at the methyl group. We report on the biochemical and structural characterizations of NsrQ, and its homologue Dcr3, from Diaporthe longicolla. The crystal structures of NsrQ and Dcr3 revealed their similar overall structures, with a cone‐shaped α+β barrel fold, to those of the nuclear transport factor 2‐like superfamily enzymes. Furthermore, the structures of Dcr3 and NsrQ variants complexed with substrate analogues and the site‐directed mutagenesis studies identified the catalytic residues and the important hydrophobic residues in shaping the active site pocket for substrate binding. These enzymes thus utilize Glu and His residues as acid‐base catalysts. Based on these observations, we proposed a detailed reaction mechanism for NsrQ‐catalyzed isomerization reactions. The novel isomerase NsrQ from Aspergillus novofumigatus is a key enzyme for the structural diversification of the fungal tetrahydroxanthones. The crystal structures of NsrQ and its homologue Dcr3 in complex with substrate analogues provided a structural basis for the dual isomerization reactions. These findings will lead to mechanistic understanding of the diversification and the stereochemical control in tetrahydroxanthone biosynthesis.