58-98-0Relevant articles and documents
Analysis of the Mildiomycin Biosynthesis Gene Cluster in Streptoverticillum remofaciens ZJU5119 and Characterization of MilC, a Hydroxymethyl cytosyl-glucuronic Acid Synthase
Wu, Jun,Li, Li,Deng, Zixin,Zabriskie, T. Mark,He, Xinyi
, p. 1613 - 1621 (2012)
Mildiomycin (MIL) is a peptidyl-nucleoside antibiotic produced by Streptoverticillum remofaciens ZJU5119 that exhibits strong inhibitory activity against powdery mildew. The entire MIL biosynthesis gene cluster was cloned and expressed in Streptomyces lividans 1326. Systematic gene disruptions narrowed down the cluster to 16 functional ORFs and identified the boundaries of the gene cluster. A putative cytosylglucuronic acid (CGA) synthase gene, milC, was disrupted in Sv. remofaciens and heterologously expressed in E. coli. An in vitro assay revealed that purified MilC could utilize either cytosine or hydroxymethylcytosine as substrate to yield CGA or hydroxymethyl-CGA (HM-CGA), respectively. MilG is believed to be a key enzyme in the MIL biosynthesis pathway and contains the CXXXCXXC motif characteristic of members of the radical S-adenosyl methionine (SAM) superfamily. Disruption of milG leads to accumulation of HM-CGA. Labeling experiments with 13C6-L-arginine indicated that decarboxylation at C5 of the pyranoside ring was coupled with the attachment of 5-guanidino-2,4-dihydroxyvalerate side chain through C-C bond formation. In contrast, exogenous 13C6-labeled 4-hydroxy-L-arginine was not incorporated into the MIL structure. Comparative analysis of the 16 MIL ORFs with counterparts involved in the biosynthesis of the structurally similar compound blasticidin S, along with the results above, provide insight into the complete MIL biosynthetic pathway.
Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics
Cui, Zheng,Liu, Xiaodong,Overbay, Jonathan,Cai, Wenlong,Wang, Xiachang,Lemke, Anke,Wiegmann, Daniel,Niro, Giuliana,Thorson, Jon S.,Ducho, Christian,Van Lanen, Steven G.
, p. 7239 - 7249 (2018/05/29)
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 nucleotidyltransfer reaction occurring after the Mur20-catalyzed aminotransfer reaction; and (iv) the bona fide sugar acceptor for Mur19 is (5′S,6′S)-GlyU, suggesting that ribosyltransfer occurs prior to N-alkylation of GlyU. Finally, a one-pot, six-enzyme reaction was utilized to generate the ADR-GlyU disaccharide core starting from UMP.
METHOD FOR PRODUCING P1,P4-DI(URIDINE 5'-)TETRAPHOSPHATE
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Page/Page column 0056, (2015/11/24)
A method for producing P1,P4-di(uridine 5'-)tetraphosphate (UP4U) that can avoid reduction of the synthetic efficiency without using UTP free is developed. A method for producing UP4U comprising reacting a phosphoric acid-activating compound represented by formula [II] or [III] with a phosphoric acid compound selected from the group consisting of UMP, UDP, UTP and a pyrophosphoric acid or a salt thereof (excluding UTP free) in water or a hydrophilic organic solvent, in the presence of a metal ion selected from the group consisting of an iron (II) ion, an iron (III) ion, a trivalent aluminum ion, a trivalent lanthanum ion, and a trivalent cerium ion. where, in the formula [II], R1 represents a uridyl group binding to the 5'-position, X represents a heterocyclic group, and n represents an integer of 1 or 2, where, in the formula [III], X represents a heterocyclic group selected from the group consisting of an imidazolyl group, a benzimidazolyl group, and a 1,2,4-triazolyl group.