Open AccessA mixed-valent Fe(II)Fe(III) species converts cysteine to an oxazolone/thioamide pair in methanobactin biosynthesis
Author(s) -
Yun Ji Park,
Richard J. Jodts,
Jeffrey W. Slater,
Reyvin M. Reyes,
Valerie J. Winton,
Rana Montaser,
Paul M. Thomas,
William B. Dowdle,
Anahi Ruiz,
Neil L. Kelleher,
J. Martin Bollinger,
Carsten Krebs,
Brian M. Hoffman,
Amy C. Rosenzweig
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2123566119
Subject(s) - thioamide , oxazolone , chemistry , biosynthesis , cysteine , enzyme , penicillamine , dehydroalanine , peptide , biochemistry , stereochemistry , active site , denticity , selenocysteine , combinatorial chemistry , metal , organic chemistry
Significance Methanobactins (Mbns), copper-binding peptidic compounds produced by some bacteria, are candidate therapeutics for human diseases of copper overload. The paired oxazolone-thioamide bidentate ligands of methanobactins are generated from cysteine residues in a precursor peptide, MbnA, by the MbnBC enzyme complex. MbnBC activity depends on the presence of iron and oxygen, but the catalytically active form has not been identified. Here, we provide evidence that a dinuclear Fe(II)Fe(III) center in MbnB, which is the only representative of a >13,000-member protein family to be characterized, is responsible for this reaction. These findings expand the known roles of diiron enzymes in biology and set the stage for mechanistic understanding, and ultimately engineering, of the MbnBC biosynthetic complex.