Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Fosfomycin: Difference between pages

{{Short description|Chemical compound}}

{{Distinguish|Fosmidomycin}}

{{Use dmy dates|date=March 2024}}

{{Infobox drug

| verifiedrevid = 461113563

| image = Fosfomycin.svg

| width = 125

| alt = Structural formula of fosfomycin

| image2 = Fosfomycin 3D ball.png

| width2 = 150

| alt2 = Ball-and-stick model of the fosfomycin molecule

| tradename = Monuril, Monurol, Ivozfo, others

| synonyms = Phosphomycin, phosphonomycin, fosfomycin tromethamine

| Drugs.com = {{drugs.com|monograph|fosfomycin-tromethamine}}

| DailyMedID = Fosfomycin

| routes_of_administration = [[Intravenous]], [[Oral administration|By mouth]]

| ATC_prefix = J01

| ATC_suffix = XX01

| ATC_supplemental = {{ATC|S02|AA17}}

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | access-date=9 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410060848/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | url-status=live }}</ref><ref>{{cite web | title=Prescription medicines and biologicals: TGA annual summary 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-and-biologicals-tga-annual-summary-2017 | access-date=31 March 2024}}</ref>

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Ivozfo | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00585 | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607033656/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00585 | url-status=live }}</ref>

| legal_UK = POM

| legal_UK_comment = <ref>{{cite web | title=Monuril 3g granules for oral solution - Summary of Product Characteristics (SmPC) | website=(emc) | date=1 June 2021 | url=https://www.medicines.org.uk/emc/product/7329 | access-date=7 June 2022 | archive-date=8 March 2022 | archive-url=https://web.archive.org/web/20220308045244/https://www.medicines.org.uk/emc/product/7329 | url-status=live }}</ref><ref>{{cite web | title=Fomicyt 40 mg/mL powder for solution for infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 February 2021 | url=https://www.medicines.org.uk/emc/product/11249/smpc | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607034149/https://www.medicines.org.uk/emc/product/11249/smpc | url-status=live }}</ref>

| legal_US_comment = <ref>{{cite web | title=Monurol- fosfomycin tromethamine powder | website=DailyMed | date=24 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad155d62-9b49-4a50-a2ae-d3aad8155936 | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607034150/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad155d62-9b49-4a50-a2ae-d3aad8155936 | url-status=live }}</ref>

| legal_status =

| bioavailability = 30–37% (by mouth, fosfomycin [[Tris|tromethamine]]); varies with food intake

| excretion = [[Kidney]], unchanged

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_supplemental = <br />{{CAS|78964-85-9}} (tromethamine salt)

| KEGG2 = D00925

<!-- | KEGG3 = D02187 -->

| IUPAC_name = [(2''R'',3''S'')-3-methyloxiran-2-yl]phosphonic acid

| C=3 | H=7 | O=4 | P=1

| melting_point = 94

<!-- Definition and medical sues -->

'''Fosfomycin''', sold under the brand name '''Monurol''' among others, is an [[antibiotic]] primarily used to treat lower [[urinary tract infections]].<ref name=AHFS2019>{{cite web |title=Fosfomycin Tromethamine Monograph for Professionals |url=https://www.drugs.com/monograph/fosfomycin-tromethamine.html |website=Drugs.com |access-date=29 October 2019 |language=en |archive-date=29 October 2019 |archive-url=https://web.archive.org/web/20191029141009/https://www.drugs.com/monograph/fosfomycin-tromethamine.html |url-status=live }}</ref> It is not indicated for [[kidney infections]].<ref name=AHFS2019/> Occasionally it is used for [[prostate infections]].<ref name=AHFS2019/> It is generally taken by mouth.<ref name=AHFS2019/>

<!-- Side effects and mechanism -->

Common side effects include diarrhea, nausea, headache, and [[vaginal yeast infections]].<ref name=AHFS2019/> Severe side effects may include [[anaphylaxis]] and [[Clostridioides difficile infection|''Clostridioides difficile''-associated diarrhea]].<ref name=AHFS2019/> While use during [[pregnancy]] has not been found to be harmful, such use is not recommended.<ref name=Preg2019>{{cite web |title=Fosfomycin (Monurol) Use During Pregnancy |url=https://www.drugs.com/pregnancy/fosfomycin.html |website=Drugs.com |access-date=29 October 2019 |language=en |archive-date=29 October 2019 |archive-url=https://web.archive.org/web/20191029141010/https://www.drugs.com/pregnancy/fosfomycin.html |url-status=live }}</ref> A single dose when breastfeeding appears safe.<ref name=Preg2019/> Fosfomycin works by interfering with the production of the [[bacterial cell wall]].<ref name=AHFS2019/>

<!-- History and culture -->

Fosfomycin was discovered in 1969 and approved for medical use in the United States in 1996 {{Globalize inline|date=February 2021}}.<ref name=AHFS2019/><ref name=Fin2010>{{cite book | vauthors = Finch RG, Greenwood D, Whitley RJ, Norrby SR |title=Antibiotic and Chemotherapy E-Book |date=2010 |publisher=Elsevier Health Sciences |isbn=9780702047657 |page=259 |url=https://books.google.com/books?id=DE4Mxc3aesEC&pg=PA259 |language=en}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> The World Health Organization classifies fosfomycin as critically important for human medicine.<ref>{{cite book | vauthors=((World Health Organization)) | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | hdl=10665/312266 | isbn=9789241515528 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=560–561|edition=76}}</ref> It was originally produced by certain types of ''[[Streptomyces]]'', although it is now made chemically.<ref name=Fin2010/>

==Medical uses==

Fosfomycin is used to treat [[bladder infections]], where it is usually given as a single dose by mouth.<ref name="pmid9098664">{{cite journal | vauthors = Patel SS, Balfour JA, Bryson HM | title = Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections | journal = Drugs | volume = 53 | issue = 4 | pages = 637–656 | date = April 1997 | pmid = 9098664 | doi = 10.2165/00003495-199753040-00007 | s2cid = 46972404 }}</ref>

Oral fosfomycin is not recommended for children under 12 years old.<ref>{{cite web |url=https://www.drugs.com/uk/monuril-sachets-3g-leaflet.html |title=MONURIL SACHETS 3G |access-date=26 May 2014 |archive-date=28 May 2014 |archive-url=https://web.archive.org/web/20140528005757/http://www.drugs.com/uk/monuril-sachets-3g-leaflet.html |url-status=live }}</ref>

Additional uses have been proposed.<ref name="pmid18444827">{{cite journal | vauthors = Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI | title = Fosfomycin: use beyond urinary tract and gastrointestinal infections | journal = Clinical Infectious Diseases | volume = 46 | issue = 7 | pages = 1069–1077 | date = April 2008 | pmid = 18444827 | doi = 10.1086/527442 | doi-access = free }}</ref> The global problem of advancing [[antimicrobial resistance]] has led to a renewed interest in its use more recently.<ref>{{cite journal | vauthors = Falagas ME, Grammatikos AP, Michalopoulos A | title = Potential of old-generation antibiotics to address current need for new antibiotics | journal = Expert Review of Anti-Infective Therapy | volume = 6 | issue = 5 | pages = 593–600 | date = October 2008 | pmid = 18847400 | doi = 10.1586/14787210.6.5.593 | s2cid = 13158593 }}</ref>

Fosfomycin can be used as an efficacious treatment for both UTIs and complicated UTIs including acute pyelonephritis. The standard regimen for complicated UTIs is an oral 3 g dose administered once every 48 or 72 hours for a total of 3 doses or a 6&nbsp;g dose every 8 hours for 7–14 days when fosfomycin is given in IV form.<ref name="Zhanel Zhanel Karlowsky 2020 pp. 1–11">{{cite journal | vauthors = Zhanel GG, Zhanel MA, Karlowsky JA | title = Oral and Intravenous Fosfomycin for the Treatment of Complicated Urinary Tract Infections | journal = The Canadian Journal of Infectious Diseases & Medical Microbiology | volume = 2020 | pages = 8513405 | date = 28 March 2020 | pmid = 32300381 | pmc = 7142339 | doi = 10.1155/2020/8513405 | publisher = Hindawi Limited | doi-access = free }}</ref>

Intravenous fosfomycin is being increasingly used for treating infections caused by [[multidrug-resistant bacteria]], mostly as a partner drug in order to avoid the occurrence of resistances and to take advantage of its synergistic activity with several other antimicrobials. Daily adult dose usually ranges from 12 to 24 grams.<ref name="Fosfomycin as Partner Drug for Syst">{{cite journal | vauthors = Antonello RM, Principe L, Maraolo AE, Viaggi V, Pol R, Fabbiani M, Montagnani F, Lovecchio A, Luzzati R, Di Bella S | display-authors = 6 | title = Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies | journal = Antibiotics | volume = 9 | issue = 8 | pages = 500 | date = August 2020 | pmid = 32785114 | pmc = 7460049 | doi = 10.3390/antibiotics9080500 | doi-access = free }}</ref> When administered in continuous infusion, a [[loading dose]] of fosfomycin 8&nbsp;g followed by a daily dose of 16&nbsp;g or 24&nbsp;g. Continuous infusion is suggested in patients with normal renal function.<ref>{{cite journal | vauthors = Antonello RM, Di Bella S, Maraolo AE, Luzzati R | title = Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies | journal = European Journal of Clinical Microbiology & Infectious Diseases | volume = 40 | issue = 6 | pages = 1117–1126 | date = June 2021 | pmid = 33604721 | pmc = 8139892 | doi = 10.1007/s10096-021-04181-x }}</ref>

===Bacterial sensitivity===

The fosfomycin molecule has an [[epoxide]] or oxirane ring, which is highly [[ring strain|strained]] and thus very reactive.{{citation needed|date=February 2023}}

Fosfomycin has broad antibacterial activity against both Gram-positive and Gram-negative pathogens, with useful activity against ''E. faecalis'', ''E. coli'', and various Gram-negatives such as '' Citrobacter'' and ''Proteus''. Given a greater activity in a low-pH milieu, and predominant excretion in active form into the urine, fosfomycin has found use for the prophylaxis and treatment of UTIs caused by these uropathogens. Of note, activity against ''S. saprophyticus'', ''Klebsiella'', and ''Enterobacter'' is variable and should be confirmed by [[minimum inhibitory concentration]] testing.

Activity against [[Beta-lactamase#Extended-spectrum beta-lactamase (ESBL)|extended-spectrum β-lactamase]]-producing pathogens, notably ESBL-producing ''E. coli'', is good to excellent, because the drug is not affected by cross-resistance issues.

Existing clinical data support use in uncomplicated UTIs, caused by susceptible organisms. However, susceptibility break-points of 64&nbsp;mg/L should not be applied for systemic infections.{{citation needed|date=February 2023}}

=== Resistance ===

Development of bacterial resistance under therapy is a frequent occurrence and makes fosfomycin unsuitable for sustained therapy of severe infections. Mutations that inactivate the nonessential glycerophosphate transporter render bacteria resistant to fosfomycin.<ref name="navas">{{cite journal | vauthors = Navas J, León J, Arroyo M, García Lobo JM | title = Nucleotide sequence and intracellular location of the product of the fosfomycin resistance gene from transposon Tn2921 | journal = Antimicrobial Agents and Chemotherapy | volume = 34 | issue = 10 | pages = 2016–2018 | date = October 1990 | pmid = 1963292 | pmc = 171982 | doi = 10.1128/AAC.34.10.2016 }}</ref><ref>{{cite journal | vauthors = Kahan FM, Kahan JS, Cassidy PJ, Kropp H | title = The mechanism of action of fosfomycin (phosphonomycin) | journal = Annals of the New York Academy of Sciences | volume = 235 | pages = 364–386 | date = May 1974 | issue = 1 | pmid = 4605290 | doi = 10.1111/j.1749-6632.1974.tb43277.x | s2cid = 33013586 | bibcode = 1974NYASA.235..364K }}</ref><ref>{{cite journal | vauthors = Castañeda-García A, Blázquez J, Rodríguez-Rojas A | title = Molecular Mechanisms and Clinical Impact of Acquired and Intrinsic Fosfomycin Resistance | journal = Antibiotics | volume = 2 | issue = 2 | pages = 217–236 | date = April 2013 | pmid = 27029300 | pmc = 4790336 | doi = 10.3390/antibiotics2020217 | doi-access = free }}</ref> Still, fosfomycin can be used to treat MRSA bacteremia.<ref name="pmid37922987">{{cite journal |vauthors=Omori K, Kitagawa H, Takada M, Maeda R, Nomura T, Kubo Y, Shigemoto N, Ohge H |title=Fosfomycin as salvage therapy for persistent methicillin-resistant Staphylococcus aureus bacteremia: A case series and review of the literature |journal=J Infect Chemother |volume=30 |issue=4 |pages=352–356 |date=April 2024 |pmid=37922987 |doi=10.1016/j.jiac.2023.10.024}}</ref>

Prescribing fosfomycin together with at least another active drug reduces the risk of developing bacterial resistance. Fosfomycin acts synergistically with many other antibiotics, including aminoglycosides, carbapenems, cephalosporins, daptomycin and oritavancin.<ref name="Fosfomycin as Partner Drug for Syst"/><ref>{{cite journal | vauthors = Lagatolla C, Mehat JW, La Ragione RM, Luzzati R, Di Bella S | title = In Vitro and In Vivo Studies of Oritavancin and Fosfomycin Synergism against Vancomycin-Resistant ''Enterococcus faecium'' | journal = Antibiotics | volume = 11 | issue = 10 | pages = 1334 | date = September 2022 | pmid = 36289992 | pmc = 9598191 | doi = 10.3390/antibiotics11101334 | doi-access = free }}</ref>

[[Enzyme]]s conferring resistance to fosfomycin have also been identified and are encoded both [[chromosome|chromosomally]] and on [[plasmid]]s.<ref name="rigsby">{{cite book | vauthors = Rigsby RE, Fillgrove KL, Beihoffer LA, Armstrong RN | chapter = Fosfomycin resistance proteins: a nexus of glutathione transferases and epoxide hydrolases in a metalloenzyme superfamily | volume = 401 | pages = [https://archive.org/details/gluthionetransfe00sies/page/367 367–379] | year = 2005 | pmid = 16399398 | doi = 10.1016/S0076-6879(05)01023-2 | isbn = 9780121828066 | series = Methods in Enzymology | title = {{sic|nolink=y|reason=error in source|Gluthione}} Transferases and Gamma-Glutamyl Transpeptidases | chapter-url = https://archive.org/details/gluthionetransfe00sies/page/367 }}</ref>

Three related fosfomycin resistance enzymes (named FosA, FosB, and FosX) are members of the [[Lactoylglutathione lyase#Structure|glyoxalase]] superfamily. These enzymes function by nucleophilic attack on carbon 1 of fosfomycin, which opens the epoxide ring and renders the drug ineffective.{{citation needed|date=February 2023}}

The enzymes differ by the identity of the nucleophile used in the reaction: [[glutathione]] for FosA, [[bacillithiol]] for FosB,<ref name="pmid21751306">{{cite journal | vauthors = Sharma SV, Jothivasan VK, Newton GL, Upton H, Wakabayashi JI, Kane MG, Roberts AA, Rawat M, La Clair JJ, Hamilton CJ | display-authors = 6 | title = Chemical and Chemoenzymatic syntheses of bacillithiol: a unique low-molecular-weight thiol amongst low G + C Gram-positive bacteria | journal = Angewandte Chemie | volume = 50 | issue = 31 | pages = 7101–7104 | date = July 2011 | pmid = 21751306 | doi = 10.1002/anie.201100196 }}</ref><ref name="pmid23256780">{{cite journal | vauthors = Roberts AA, Sharma SV, Strankman AW, Duran SR, Rawat M, Hamilton CJ | title = Mechanistic studies of FosB: a divalent-metal-dependent bacillithiol-S-transferase that mediates fosfomycin resistance in Staphylococcus aureus | journal = The Biochemical Journal | volume = 451 | issue = 1 | pages = 69–79 | date = April 2013 | pmid = 23256780 | pmc = 3960972 | doi = 10.1042/BJ20121541 }}</ref> and water for FosX.<ref name="rigsby" />

In general, FosA and FosX enzymes are produced by Gram-negative bacteria, whereas FosB is produced by Gram-positive bacteria.<ref name="rigsby" />

FosC uses [[Adenosine triphosphate|ATP]] and adds a [[phosphate]] group to fosfomycin, thus altering its properties and making the drug ineffective.<ref name="pmid7492106">{{cite journal | vauthors = García P, Arca P, Evaristo Suárez J | title = Product of fosC, a gene from Pseudomonas syringae, mediates fosfomycin resistance by using ATP as cosubstrate | journal = Antimicrobial Agents and Chemotherapy | volume = 39 | issue = 7 | pages = 1569–1573 | date = July 1995 | pmid = 7492106 | pmc = 162783 | doi = 10.1128/aac.39.7.1569 }}</ref>

==Side effects==

The drug is well tolerated and has a low incidence of harmful side effects.<ref name="pmid9098664"/>

==Mechanism of action==

Despite its name (ending in -omycin) Fosfomycin is not a [[macrolide]], but a member of a novel class of phosphonic antibiotics. Fosfomycin is bactericidal and inhibits bacterial cell wall biogenesis by inactivating the enzyme [[UDP-N-acetylglucosamine enolpyruvyl transferase|UDP-''N''-acetylglucosamine-3-enolpyruvyltransferase]], also known as MurA.<ref name="Brown">{{cite journal | vauthors = Brown ED, Vivas EI, Walsh CT, Kolter R | title = MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli | journal = Journal of Bacteriology | volume = 177 | issue = 14 | pages = 4194–4197 | date = July 1995 | pmid = 7608103 | pmc = 177162 | doi = 10.1128/jb.177.14.4194-4197.1995 }}</ref> This enzyme catalyzes the [[committed step]] in [[peptidoglycan]] biosynthesis, namely the ligation of [[phosphoenolpyruvate]] (PEP) to the 3'-hydroxyl group of [[Uridine diphosphate N-acetylglucosamine|UDP-''N''-acetylglucosamine]]. This pyruvate moiety provides the linker that bridges the glycan and peptide portion of peptidoglycan. Fosfomycin is a PEP analog that inhibits MurA by [[alkylation|alkylating]] an active site [[cysteine]] residue (Cys 115 in the ''[[Escherichia coli]]'' enzyme).<ref>{{cite journal | vauthors = Zhu JY, Yang Y, Han H, Betzi S, Olesen SH, Marsilio F, Schönbrunn E | title = Functional consequence of covalent reaction of phosphoenolpyruvate with UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) | journal = The Journal of Biological Chemistry | volume = 287 | issue = 16 | pages = 12657–12667 | date = April 2012 | pmid = 22378791 | pmc = 3339971 | doi = 10.1074/jbc.M112.342725 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Krekel F, Samland AK, Macheroux P, Amrhein N, Evans JN | title = Determination of the pKa value of C115 in MurA (UDP-N-acetylglucosamine enolpyruvyltransferase) from Enterobacter cloacae | journal = Biochemistry | volume = 39 | issue = 41 | pages = 12671–12677 | date = October 2000 | pmid = 11027147 | doi = 10.1021/bi001310x }}</ref>

Fosfomycin enters the bacterial cell through the glycerophosphate transporter.<ref name="santoro">{{cite journal | vauthors = Santoro A, Cappello AR, Madeo M, Martello E, Iacopetta D, Dolce V | title = Interaction of fosfomycin with the glycerol 3-phosphate transporter of Escherichia coli | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1810 | issue = 12 | pages = 1323–1329 | date = December 2011 | pmid = 21791237 | doi = 10.1016/j.bbagen.2011.07.006 }}</ref>

==History==

Fosfomycin (originally known as phosphonomycin) was discovered in a joint effort of [[Merck and Co.]] and Spain's Compañía Española de Penicilina y Antibióticos (CEPA). It was first isolated by screening broth cultures of ''[[Streptomyces fradiae]]'' isolated from soil samples for the ability to cause formation of [[spheroplasts]] by growing bacteria. The discovery was described in a series of papers published in 1969.<ref name=:1>{{cite book | vauthors = Silver LL | chapter = Rational Approaches to Antibacterial Discovery: Pre-Genomic Directed and Phenotypic Screening | veditors = Dougherty T, Pucci MJ |title= Antibiotic Discovery and Development |publisher=Springer |date=2011 |pages=46 |isbn=978-1-4614-1400-1|doi=10.1007/978-1-4614-1400-1_2}}</ref> CEPA began producing fosfomycin on an industrial scale in 1971 at its [[Aranjuez]] facility.<ref>{{cite web | work = Encros | url = http://www.ercros.es/eng/internas.asp?arxiu=qh_aranjuezh |title = About us: Our history | archive-url = https://web.archive.org/web/20110914142734/http://www.ercros.es/eng/internas.asp?arxiu=qh_aranjuezh | archive-date= 14 September 2011 }}</ref>

==Manufacture==

The complete fosfomycin biosynthetic [[gene cluster]] from ''Streptomyces fradiae'' has been cloned and sequenced and the heterologous production of fosfomycin in ''S. lividans'' has been achieved by Ryan Woodyer of the [[Huimin Zhao]] and [[Wilfred van der Donk]] research groups.<ref name="pmid17113999">{{cite journal | vauthors = Woodyer RD, Shao Z, Thomas PM, Kelleher NL, Blodgett JA, Metcalf WW, van der Donk WA, Zhao H | display-authors = 6 | title = Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster | journal = Chemistry & Biology | volume = 13 | issue = 11 | pages = 1171–1182 | date = November 2006 | pmid = 17113999 | doi = 10.1016/j.chembiol.2006.09.007 | doi-access = free }}</ref>

Large scale production of fosfomycin is achieved by making an [[epoxide]] of cis-propenylphosphonic acid to yield [[racemic mixture]] fosfomycin.<ref name="Marocco Davis Finnell Nguyen 2011 pp. 1784–1789">{{cite journal | vauthors = Marocco CP, Davis EV, Finnell JE, Nguyen PH, Mateer SC, Ghiviriga I, Padgett CW, Feske BD | display-authors = 6 | title=Asymmetric synthesis of (−)-fosfomycin and its trans-(1S,2S)-diastereomer using a biocatalytic reduction as the key step | journal=Tetrahedron: Asymmetry | publisher=Elsevier BV | volume=22 | issue=18–19 | year=2011 | issn=0957-4166 | doi=10.1016/j.tetasy.2011.10.009 | pages=1784–1789}}</ref>

== References ==

{{reflist}}

{{Cell wall disruptive antibiotics}}

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[[Category:Antibiotics]]

[[Category:Phosphonic acids]]

[[Category:Epoxides]]

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[[Category:Wikipedia medicine articles ready to translate]]