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DOI	10.1073/pnas.2019863118
	Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily
	Simon M.A.; Ongpipattanakul C.; Nair S.K.; van der Donk W.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:23
英文摘要	The epoxide-containing phosphonate natural product fosfomycin is a broad-spectrum antibiotic used in the treatment of cystitis. Fosfomycin is produced by both the plant pathogen Pseudomonas syringae and soil-dwelling streptomycetes. While the streptomycete pathway has recently been fully elucidated, the pseudomonad pathway is still mostly elusive. Through a systematic evaluation of heterologous expression of putative biosynthetic enzymes, we identified the central enzyme responsible for completing the biosynthetic pathway in pseudomonads. The missing transformation involves the oxidative decarboxylation of the intermediate 2-phosphonomethylmalate to a new intermediate, 3-oxo-4-phosphonobutanoate, by PsfC. Crystallographic studies reveal that PsfC unexpectedly belongs to a new class of diiron metalloenzymes that are part of the polymerase and histidinol phosphatase superfamily. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Decarboxylase; Fosfomycin; Metallohydrolase; Nonheme iron; Phosphonate
语种	英语
scopus关键词	2 phosphonomethylmalate; 3 oxo 4 phosphonobutanoate; butyric acid; fosfomycin; hydrolase; malic acid; metallohydrolase; unclassified drug; Article; bacterial gene; biosynthesis; catalysis; controlled study; crystal structure; crystallography; decarboxylation; enzyme activity; gene expression; gene sequence; in vitro study; mutagenesis; nonhuman; oxidative decarboxylation; protein expression; protein structure; Pseudomonadaceae; psfC gene
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238532
作者单位	Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; HHMI, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
推荐引用方式 GB/T 7714	Simon M.A.,Ongpipattanakul C.,Nair S.K.,et al. Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily[J],2021,118(23).
APA	Simon M.A.,Ongpipattanakul C.,Nair S.K.,&van der Donk W.A..(2021).Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA	Simon M.A.,et al."Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).