Ivermectin B1a

Streptomyces avermitilis industrial strain as cell factory for Ivermectin B1a production.[Pubmed:30623120]

Synth Syst Biotechnol. 2018 Dec 27;4(1):34-39.

Ivermectin, a kind of valuable derivatives of Avermectin, is distinct from Avermectin due to the saturated bond at C22-C23 position. Combinatorial biosynthesis of Ivermectins based on Avermectins biosynthetic gene cluster (ave) has been achieved recently, while the establishment of an Ivermectin homogeneous component producing strain is challenging because of the limited compatibility between the native and heterologous polyketide synthase (PKS) domains. In this study, the PKS module 2 Dehydratase (DH)-Enoylreductase (ER)-Ketoreductase (KR) domain set of Meilingmycin, which is another naturally occurring homologue of Avermectin, was employed to substitute the DH-KR domains of Avermectins PKS module 2 to generate an Ivermectin biosynthetic gene cluster (ive). Ivermectins B1a and A1a were heterologously biosynthesized in a classic actinomyces host Streptomyces lividans. The Avermectin B1a high-producing strain S. avermitilis 3-115 was genetically engineered to give an artificial host cell and Ivermectin B1a single component was effectively produced with a production of 1.25+/-0.14g/L.

Ivermectin efficacy against Biomphalaria, intermediate host snail vectors of Schistosomiasis.[Pubmed:28293033]

J Antibiot (Tokyo). 2017 May;70(5):680-684.

The impact of ivermectin on adult snails of the genus Biomphalaria (B. glabrata, B. tenagophila and B. straminea), B. glabrata infected with Schistosoma mansoni, snail egg-masses cercariae and miracidia, as well as on guppy fish (Poecilia reticulata) was examined and evaluated. Biomphalaria snails, egg-masses, parasite stages and guppies were all exposed to different concentrations of ivermectin for 24 h, followed by regular observations of mortality. The calculated lethal doses of ivermectin were around an LD50 of 0.03 mug ml(-1), and an LD90 of 0.3 mug ml(-1) for the three species of snails. Specimens of B. glabrata actually shedding parasite cercariae all died when exposed to ivermectin at a concentration of a mere 0.01 mug ml(-1). Ivermectin B1a, the major (80%) component of commercially available ivermectin, proved to be inactive, and it was the minor (20%) component, ivermectin B1b, which caused snail death. Snail egg-masses were not affected, even at the highest concentration of 100 mug ml(-1). With respect to S. mansoni parasite stages, 0.2 mug ml(-1) ivermectin killed 50% of cercariae and miracidia within five minutes, rising to 90% after 30 min. Mortality of guppy fish within 24 h of exposure to ivermectin at concentrations of 0.5 mug ml(-1) and 0.01 mug ml(-1), were 100% and 30%, respectively. The concentration of 0.01 mug ml(-1) that killed Schistosoma mansoni-infected snails only caused 30% mortality in guppy fish. Ivermectin can be considered a promising molluscicide, especially as it is more potent against infected snails than uninfected ones, although it has no impact on egg-masses. Ivermectin and its derivatives could be explored in the search for a new agent to help control schistosomiasis transmission.