Themilbemycins are a group ofmacrolides chemically related to theavermectins and were first isolated in 1972 fromStreptomyces hygroscopicus.They are used in veterinary medicine asantiparasitic agents against worms, ticks and fleas.[1] They also showinsecticidal andacaricidal activity.[2]
Milbemycins have a similar mechanism of action, but a longer half-life than the avermectins. They openglutamate-sensitivechloride channels inneurons andmyocytes ofinvertebrates, leading tohyperpolarisation of these cells and blocking of signal transfer.[2] They are inIRAC class 6.[3]
Milbemycin is effective against some avermectin-resistant insects.[4]
Like avermectins, milbemycins are products offermentation byStreptomyces species. A grand total of five species, namelyS. hygroscopicus,S. griseochromogenes,S. cyaneogriseus,S. nanchanggensis andS. bingchenggensis, are known to produce this family of compounds.[4]
The biosynthetic cluster fromS. bingchenggensis andS. 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.[4]
An alternative pathway to higher yields was demonstrated in 2017, when select genes fromS. avermitilis were swapped out so the avermectin producer makes milbemycin instead.[4]
 |
| Name | =R1 | =R2 | –R3 |
|---|---|---|---|
| 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[1] |
| Nemadectin | –H, (β)–OH | –H, (α)–OH | (Z)–C(CH3)=CH–CH(CH3)2[1] |
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