Biosynthetic Studies of Phomopsins Unveil Posttranslational Installation of Dehydroamino Acids by UstYa Family Proteins

UstYa family proteins (DUF3328) are widely and specifically distributed in fungi. They are known to be involved in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and nonribosomal peptides, and possibly catalyze various reactions, including oxidative cyc...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-12, Vol.60 (49), p.25729-25734
Main Authors: Sogahata, Kaho, Ozaki, Taro, Igarashi, Yuya, Naganuma, Yuka, Liu, Chengwei, Minami, Atsushi, Oikawa, Hideaki
Format: Article
Language:English
Subjects:
Amino acid sequence
Amino acids
Amino Acids - chemistry
Amino Acids - metabolism
Aspergillus oryzae - chemistry
Biosynthesis
Chemical reactions
Desaturation
enzymes
Fungal Proteins - chemistry
Fungal Proteins - metabolism
Fungi
Genomes
halogenation
Homology
Metabolites
Molecular Structure
Mycotoxins - biosynthesis
Mycotoxins - chemistry
natural products
Network analysis
Peptides
Protein Processing, Post-Translational
Proteins
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Summary:UstYa family proteins (DUF3328) are widely and specifically distributed in fungi. They are known to be involved in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and nonribosomal peptides, and possibly catalyze various reactions, including oxidative cyclization and chlorination. In this study, we focused on phomopsin A, a fungal RiPP consisting of unique nonproteinogenic amino acids. Gene knockout experiments demonstrated that three UstYa homologues, phomYc, phomYd, and phomYe, are essential for the desaturation of amino acid moieties, showing unprecedented function among UstYa family proteins. Sequence similarity network analysis indicated that their amino acid sequences are highly diverged and that most remain uncharacterized, paving the way for genome mining of fungal metabolites with unique modifications. The biosynthesis of the fungal ribosomally synthesized and posttranslationally modified peptide phomopsin was elucidated by gene inactivation experiments. Notably, chlorination by tyrosinase‐like enzyme PhomQ1 and desaturation of amino acid moieties by UstYa family (DUF3328) proteins PhomYc/Yd/Ye were uncovered. Besides the known function of UstYa homologues, this study unveiled the remarkable functional diversity of these fungi‐specific proteins.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202111076