Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics

The Journal of Organic Chemistry
Zheng CuiSteven G Van Lanen

Abstract

Muraymycins belong to a family of nucleoside antibiotics that have a distinctive disaccharide core consisting of 5-amino-5-deoxyribofuranose (ADR) attached to 6'- N-alkyl-5'- C-glycyluridine (GlyU). Here, we functionally assign and characterize six enzymes from the muraymycin biosynthetic pathway involved in the core assembly that starts from uridine monophosphate (UMP). The biosynthesis is initiated by Mur16, a nonheme Fe(II)- and α-ketoglutarate-dependent dioxygenase, followed by four transferase enzymes: Mur17, a pyridoxal-5'-phosphate (PLP)-dependent transaldolase; Mur20, an aminotransferase; Mur26, a pyrimidine phosphorylase; and Mur18, a nucleotidylyltransferase. The pathway culminates in glycosidic bond formation in a reaction catalyzed by an additional transferase enzyme, Mur19, a ribosyltransferase. Analysis of the biochemical properties revealed several noteworthy discoveries including that (i) Mur16 and downstream enzymes can also process 2'-deoxy-UMP to generate a 2-deoxy-ADR, which is consistent with the structure of some muraymycin congeners; (ii) Mur20 prefers l-Tyr as the amino donor source; (iii) Mur18 activity absolutely depends on the amine functionality of the ADR precursor consistent with the nucleotidyltra...Continue Reading

References

Feb 24, 2001·Nature·A SchmidB Witholt
Aug 29, 2002·Journal of the American Chemical Society·Leonard A McDonaldR Thomas Williamson
May 9, 2003·Natural Product Reports·Ken-ichi Kimura, Timothy D H Bugg
Aug 23, 2003·The Journal of Antibiotics·Masayuki IgarashiMasa Hamada
Jun 4, 2008·Annual Review of Biochemistry·L L LairsonS G Withers
Nov 11, 2008·Advances in Enzymology and Related Areas of Molecular Biology·Gavin J Williams, Jon S Thorson
Dec 30, 2009·Chembiochem : a European Journal of Chemical Biology·Leonard KaysserBertolt Gust
Jan 1, 2010·Chembiochem : a European Journal of Chemical Biology·Masanori FunabashiSteven G Van Lanen
Feb 11, 2010·The Journal of Organic Chemistry·Tetsuya TaninoAkira Matsuda
May 19, 2011·The Journal of Antibiotics·Yoko FujitaToshio Takatsu
Aug 9, 2011·Journal of the American Chemical Society·Xiuling ChiSteven G Van Lanen
Nov 1, 2012·Journal of the American Chemical Society·Sandra Barnard-BritsonSteven G Van Lanen
Sep 10, 2013·Angewandte Chemie·Masanori FunabashiSteven G Van Lanen
Oct 17, 2014·Chemistry : a European Journal·Anatol P SporkChristian Ducho
Mar 5, 2015·Chemical Society Reviews·Sherif I ElshahawiJon S Thorson
Sep 4, 2015·Chemical Society Reviews·Dong-Mei LiangJian-Jun Qiao
Jan 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ying HuangSteven G Van Lanen
Mar 20, 2018·Journal of Natural Products·Zheng CuiSteven G Van Lanen

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