- Mechanistic studies of HPP epoxidase: Configuration of the substrate governs its enzymatic fate
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The regiospecificity of the initial H-atom abstraction may explain the fact that HPP epoxidase, a non-heme iron-containing enzyme, catalyzes not only the conversion of (S)-HPP ((S)-1) to fosfomycin (2), but also the oxidation of the 1R enantiomer, which l
- Zhao, Zongbao,Liu, Pinghua,Murakami, Kazuo,Kuzuyama, Tomohisa,Seto, Haruo,Liu, Hung-wen
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Read Online
- A new non-chloride method of synthesis of antibacterial antibiotic fosfomycin based on the principles of green chemistry
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A new non-chloride method for synthesis of antibacterial antibiotic fosfomycin, which is based on principles of green chemistry, has been developed.
- Belakhov,Garabadzhiu
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p. 2974 - 2977
(2017/07/07)
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- Evidence for radical-mediated catalysis by HppE: A study using cyclopropyl and methylenecyclopropyl substrate analogues
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(S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and methylenecyclopropyl-containing compounds were synthesized and studied as radical clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)-isomers of the cyclopropyl-containing analogues were efficiently converted to epoxide and ketone products by HppE, respectively. In contrast, the ultrafast methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid radical-triggered ring-opening process that leads to enzyme inactivation. Taken together, these findings provide, for the first time, experimental evidence for the involvement of a C2-centered radical intermediate with a lifetime on the order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP.
- Huang, Hui,Chang, Wei-Chen,Romo, Anthony,Mansoorabadi, Steven O.,Liu, Hung-Wen,Pai, Pei-Jing,Russell, David H.
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supporting information
p. 16171 - 16174,4
(2020/09/09)
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- Apparatus And Methods For Delivering A Plurality Of Medicaments For Management Of Co-Morbid Diseases, Illnesses Or Conditions
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A method and apparatus for delivering a plurality of medicaments in a single delivery vehicle for the management of co-morbid diseases, illnesses and conditions. The present invention provides a novel delivery process for many medicaments. Medicaments may be encapsulated and stored separately within a larger capsule until the time of ingestion, consumption, or the like. Benefits of the present invention include maintaining separation of distinct ingredients within a single capsule and the capability to control the time release of multiple ingredients within the capsule.
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- Studies on the biodegradation of fosfomycin: Growth of Rhizobium huakuii PMY1 on possible intermediates synthesised chemically
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The first step of the mineralisation of fosfomycin by R. huakuii PMY1 is hydrolytic ring opening with the formation of (1R,2R)-1,2- dihydroxypropylphosphonic acid. This phosphonic acid and its three stereoisomers were synthesised by chemical means and tes
- McGrath, John W.,Hammerschmidt, Friedrich,Preusser, Werner,Quinn, John P.,Schweifer, Anna
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experimental part
p. 1944 - 1953
(2009/06/28)
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- Indirect evidence for the biosynthesis of (1S,2S)-epoxypropylphosphonic acid as a co-metabolite of fosfomycin [(1R,2S)-1,2-epoxypropylphosphonic acid] by Streptomyces fradiae
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Treatment of the culture broth of fosfomycin (1) producing Streptomyces fradae with ammonia gives 2-3% of the C-1 epimeric compound 5, as well as the known (1R,2R)-2-amino-1-hydroxypropylphosphonic acid (3) derived from fosfomycin. The configuration of 5 was determined by capillary electrophoresis employing a quinine carbamate-type chiral selector and by synthesis from a monoprotected 1,2-dihydroxypropylphosphonate of known absolute configuration. It is postulated that (1S,2R)-2-amino-1-hydroxypropylphosphonic acid (5) is derived by ring opening of a trans-epoxide, formed as a co-metabolite of fosfomycin (cis-epoxide), with ammonia. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Simov, Biljana Peric,Wuggenig, Frank,Laemmerhofer, Michael,Lindner, Wolfgang,Zarbl, Elfriede,Hammerschmidt, Friedrich
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p. 1139 - 1142
(2007/10/03)
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- Epoxypropylphosphonate salt of jesamycin and pharmaceutical composition containing same
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A new salt of the macrolide antibiotic Josamycin with (-)-cis-1,4-epoxypropionylphosphonic acid, of formula (I) STR1 The salt (I), prepared from Josamycin base and phosphomycin, possesses favorable antimicrobial and pharmacokinetics properties.
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