Isolation and Identification of Novel Macrocyclic Lactones from Streptomyces avermitilis NEAU1069 with Acaricidal and Nematocidal Activity

Abstract

Bioactivity-guided fractionation of Streptomyces avermitilis NEAU1069 fermentation broth was used to isolate and determine the chemical identity of bioactive constituents with acaricidal and nemotocidal activity. The structures of novel compounds 1 and 2 were determined on the basis of spectroscopic analysis, including 1D and 2D NMR as well as HRESI-MS, ESI-MS of spectrometry analysis, UV and IR spectroscopic analyses, and comparison with data from the literature. The acaricidal activities of the isolated compounds against adult mites and mite eggs were evaluated by mortality and unhatched eggs. The nematocidal activity of the isolated compounds against Caenorhabditis elegans was calculated according to the immobilized rates against the total number of tested nematodes. The results indicated that compounds 1 and 2 exhibited potent acaricidal activity against adult mites, with a mortality of >90% at a concentration of 30 microg/mL. However, compounds 1 and 2 showed only weak acaricidal activity against mite eggs, with unhatched mite egg rates of <60% at a concentration of 100 microg/mL. Compound 2, a hydroxylated derivative at C-23 of 1, possessed a high nematocidal activity against C. elegans, with an immobility of >90% at a concentration of 10 microg/mL. These results demonstrate that compounds 1 and 2, especially compound 2, have potential as pesticides with acaricidal and nematocidal activity.

Two new doramectin analogs from Streptomyces avermitilis NEAU1069: fermentation, isolation and structure elucidation

“…Along with previously obtained analogs of doramectin, avermectin and milbemycin from S. avermitilis NEAU1069, 3,4 we believe that these two new compounds possibly have important roles in understanding and perfecting the proposed biosynthetic pathways of avermectins and milbemycins.…”

“…3,4 The strain was maintained on a YMS medium containing soluble starch (Bei Jing Ao Bo Xing, Beijing, China) 10 g, yeast extract (Bei Jing Ao Bo Xing) 2 g, KNO 3 Two new doramectin analogs from Streptomyces avermitilis X-J Wang et al of sterile water was added to the slant of the YMS medium. The spores were scraped and transferred onto a sterile tube containing glass beads; the spore suspension was then filtered through six layers of a sterile filter cheesecloth and adjusted to 10 7 -10 8 c.f.u.…”

“…3 Later, two novel macrolide compounds with a cyclohexyl group at the position of C-25, such as doramectin and avermectin B1a, were obtained from the fermentation broth, using bioactivity guided fractionation method, on adding cyclohexanecarboxylic acid to the fermentation medium. 4 The co-existence of milbemycins and avermectin implies that S. avermitilis NEAU1069 is an interesting strain and merits further study. Therefore, large amounts of fermentation broth (30 l) were collected and the detailed constituents were investigated; two other new compounds 1 and 2 ( Figure 1), similar to doramectin, were subsequently obtained.…”

Four New Doramectin Congeners with Acaricidal and Insecticidal Activity from Streptomyces avermitilis NEAU1069

“…In our previous study, two novel macrocyclic lactones and three milbemycins, including one new compound, with acaricidal and insecticidal activities were isolated from Streptomyces avermitilis NEAU1069 [10] [11]. In further studies concerning the chemical diversity of the constituents of S. avermitilis NEAU1069, the bioassay-guided fractionation was employed to investigate the active metabolites with acaricidal activity.…”

“…1 are the presence of a,b-conjugated ketone (d(C) 199.5) in 4, and that the C(2) -C(7) aromatic moiety in 3 was replaced by a cyclohexene ring as in doramectin [11]. This was further supported by HMBC correlations of Me(32), with C(3), C(4), and C(5), of Me(33) with C(7), and of HÀC(2) with C(1) (Fig.…”