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| {{Short description|Class of chemical compounds}} | |||
| The '''milbemycins''' are a group of ]s chemically related to the ]s and were first isolated in 1972 from '']''. | The '''milbemycins''' are a group of ]s chemically related to the ]s and were first isolated in 1972 from '']''. | ||
| They are used in veterinary medicine as ] agents against worms, ticks and fleas.<ref name="ECSOC2"> {{webarchive|url=https://web.archive.org/web/20080418065116/http://ecsoc2.hcc.ru/ecsoc-2/dl001/insecticides.html |date=2008-04-18 }}</ref> | They are used in veterinary medicine as ] agents against worms, ticks and fleas.<ref name="ECSOC2"> {{webarchive|url=https://web.archive.org/web/20080418065116/http://ecsoc2.hcc.ru/ecsoc-2/dl001/insecticides.html |date=2008-04-18 }}</ref> They also show ]<nowiki/>l and ] activity.<ref name=":02">{{Cite book |last=Jeschke |first=Peter |url=https://onlinelibrary.wiley.com/doi/book/10.1002/9783527699261 |title=Modern Crop Protection Compounds |last2=Witschel |first2=Matthias |last3=Krämer |first3=Wolfgang |last4=Schirmer |first4=Ulrich |date=25 January 2019 |publisher=Wiley‐VCH |year=2019 |isbn=9783527699261 |edition=3rd |pages=1478-1500 |chapter=33.6 Glutamate‐gated Chloride Channel Allosteric Modulators: Avermectins and Milbemycins}}</ref> | ||
| __TOC__ | |||
| == Mechanism of action == | == Mechanism of action == | ||
| Milbemycins have a similar mechanism of action, but a longer half-life than the avermectins. They open ]-sensitive ]s in ]s and ]s of ]s, leading to ] of these cells and blocking of signal transfer.<ref name=":02" /> They are in ] class 6.<ref>{{cite journal |last=Sparks |first=Thomas C |last2=Storer |first2=Nicholas |last3=Porter |first3=Alan |last4=Slater |first4=Russell |last5=Nauen |first5=Ralf |date=2021 |title=Insecticide resistance management and industry: the origins and evolution of the I nsecticide R esistance A ction C ommittee (IRAC) and the mode of action classification scheme |journal=Pest Management Science |volume=77 |issue=6 |pages=2609–2619 |doi=10.1002/ps.6254 |issn=1526-498X |pmc=8248193 |pmid=33421293 |doi-access=free}}</ref> | |||
| {{Citation needed|date=July 2009}} | |||
| Milbemycin is effective against some avermectin-resistant insects.<ref name="pmid34550409"/> | |||
| == Biosynthesis == | |||
| Like avermectins, milbemycins are products of ] by '']'' species. A grand total of five species, namely '']'', '']'', '']'', '']'' and '']'', are known to produce this family of compounds.<ref name="pmid34550409">{{cite journal |last1=Yan |first1=YS |last2=Xia |first2=HY |title=Recent advances in the research of milbemycin biosynthesis and regulation as well as strategies for strain improvement. |journal=Archives of Microbiology |date=December 2021 |volume=203 |issue=10 |pages=5849–5857 |doi=10.1007/s00203-021-02575-1 |pmid=34550409|s2cid=237594779 }}</ref> | |||
| The biosynthetic cluster from ''S. bingchenggensis'' and ''S. nanchanggensis'' have been sequenced and analyzed, partly by analogy to the homologous biosynthetic cluster for avermectin. New regulatory elements that control how much milbemycins are being identified in hopes to improve the industrial fermentation yield of milbemycins, which (as of 2021) is much lower than that of avermectin.<ref name="pmid34550409"/> | |||
| An alternative pathway to higher yields was demonstrated in 2017, when select genes from ''S. avermitilis'' were swapped out so the avermectin producer makes milbemycin instead.<ref name="pmid34550409"/> | |||
| == Examples == | == Examples == | ||
| {{missing information|section|source species for examples ({{PMID|30689104}}, {{PMID|27604457}}), commercialized 5-oxo ({{PMID|30121749}})|date=October 2023}} | |||
| ] | ] | ||
| {| class="wikitable" | {| class="wikitable" | ||
Latest revision as of 20:04, 14 December 2024
Class of chemical compoundsThe milbemycins are a group of macrolides chemically related to the avermectins and were first isolated in 1972 from Streptomyces hygroscopicus. They are used in veterinary medicine as antiparasitic agents against worms, ticks and fleas. They also show insecticidal and acaricidal activity.
Mechanism of action
Milbemycins have a similar mechanism of action, but a longer half-life than the avermectins. They open glutamate-sensitive chloride channels in neurons and myocytes of invertebrates, leading to hyperpolarisation of these cells and blocking of signal transfer. They are in IRAC class 6.
Milbemycin is effective against some avermectin-resistant insects.
Biosynthesis
Like avermectins, milbemycins are products of fermentation by Streptomyces species. A grand total of five species, namely S. hygroscopicus, S. griseochromogenes, S. cyaneogriseus, S. nanchanggensis and S. bingchenggensis, are known to produce this family of compounds.
The biosynthetic cluster from S. bingchenggensis and S. nanchanggensis have been sequenced and analyzed, partly by analogy to the homologous biosynthetic cluster for avermectin. New regulatory elements that control how much milbemycins are being identified in hopes to improve the industrial fermentation yield of milbemycins, which (as of 2021) is much lower than that of avermectin.
An alternative pathway to higher yields was demonstrated in 2017, when select genes from S. avermitilis were swapped out so the avermectin producer makes milbemycin instead.
Examples
 | This section is missing information about source species for examples (PMID 30689104, PMID 27604457), commercialized 5-oxo (PMID 30121749). Please expand the section to include this information. Further details may exist on the talk page. (October 2023) |
| Name | =R | =R | –R |
|---|---|---|---|
| Milbemectin | –H, (β)–OH | –H, –H | –CH3 : –CH2CH3 = 3:7 |
| Milbemycin oxime | =NOH | –H, –H | –CH3 : –CH2CH3 = 3:7 |
| Moxidectin | –H, (β)–OH | =NOCH3 | (Z)–C(CH3)=CH–CH(CH3)2 |
| Nemadectin | –H, (β)–OH | –H, (α)–OH | (Z)–C(CH3)=CH–CH(CH3)2 |
References
- ^ The 2nd International Electronic Conference on Synthetic Organic Chemistry: Insecticides Archived 2008-04-18 at the Wayback Machine
- ^ Jeschke, Peter; Witschel, Matthias; Krämer, Wolfgang; Schirmer, Ulrich (25 January 2019). "33.6 Glutamate‐gated Chloride Channel Allosteric Modulators: Avermectins and Milbemycins". Modern Crop Protection Compounds (3rd ed.). Wiley‐VCH. pp. 1478–1500. ISBN 9783527699261.
{{cite book}}: CS1 maint: date and year (link) - Sparks, Thomas C; Storer, Nicholas; Porter, Alan; Slater, Russell; Nauen, Ralf (2021). "Insecticide resistance management and industry: the origins and evolution of the I nsecticide R esistance A ction C ommittee (IRAC) and the mode of action classification scheme". Pest Management Science. 77 (6): 2609–2619. doi:10.1002/ps.6254. ISSN 1526-498X. PMC 8248193. PMID 33421293.
- ^ Yan, YS; Xia, HY (December 2021). "Recent advances in the research of milbemycin biosynthesis and regulation as well as strategies for strain improvement". Archives of Microbiology. 203 (10): 5849–5857. doi:10.1007/s00203-021-02575-1. PMID 34550409. S2CID 237594779.
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