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Structural Basis for Isomerization Reactions in Fungal Tetrahydroxanthone Biosynthesis and Diversification
Author(s) -
Yang Jiali,
Mori Takahiro,
Wei Xingxing,
Matsuda Yudai,
Abe Ikuro
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202107884
Subject(s) - isomerization , isomerase , chemistry , stereochemistry , biosynthesis , active site , enzyme , lyase , enzyme catalysis , catalysis , biochemistry
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.