LL-F28249 antibiotic complex: A new family of antiparastic macrocyclic lactones. Isolation, characterization and structures of LL-F28249 .ALPHA., .BETA., .GAMMA., .LAMBDA..

Carter, Guy T.; Nietsche, Jeanne A.; Hertz, Martin R.; Williams, David R.; Siegel, Marshall M.; Morton, George O.; James, John C.; Borders, Donald B.

doi:10.7164/antibiotics.41.519

Cited by 66 publications

(21 citation statements)

References 4 publications

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“…Metagenomic sequencing of biosynthetic domains found in NYC park soils indicates that bacteria containing gene clusters capable of encoding either these NPs or close congeners of these NPs are likely widely distributed in park soils from a single city. Original discovery sites for molecules included on the world map in B were obtained from the following references: epothilone (32), rapamycin (33), teicoplanin (34,35), erythromycin (36), CDA (calcium-dependent antibiotic) (37), tiacumicin B (38), FR910464 (39), ascomycin (40), natamycin (41), geldanamycin (42), nemadectin (43,44). second round of clustering, 97% centroid sequences from all samples were pooled and clustered at 95% identity using Usearch cluster_fast (30).…”

Section: Methodsmentioning

confidence: 99%

Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity

Charlop–Powers

Pregitzer

Lemetre

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Numerous therapeutically relevant small molecules have been identified from the screening of natural products (NPs) produced by environmental bacteria. These discovery efforts have principally focused on culturing bacteria from natural environments rich in biodiversity. We sought to assess the biosynthetic capacity of urban soil environments using a phylogenetic analysis of conserved NP biosynthetic genes amplified directly from DNA isolated from New York City park soils. By sequencing genes involved in the biosynthesis of nonribosomal peptides and polyketides, we found that urban park soil microbiomes are both rich in biosynthetic diversity and distinct from nonurban samples in their biosynthetic gene composition. A comparison of sequences derived from New York City parks to genes involved in the biosynthesis of biomedically important NPs produced by bacteria originally collected from natural environments around the world suggests that bacteria producing these same families of clinically important antibiotics, antifungals, and anticancer agents are actually present in the soils of New York City. The identification of new bacterial NPs often centers on the systematic exploration of bacteria present in natural environments. Here, we find that the soil microbiomes found in large cities likely hold similar promise as rich unexplored sources of clinically relevant NPs.

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Section: Methodsmentioning

confidence: 99%

Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity

Charlop–Powers

Pregitzer

Lemetre

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The four major endectocides were originally designated archaemycins 1-4 but have been independently reported from another Streptomyces species, Streptomyces cyaneogriseus subsp. noncyanogenus, and the compounds referred to as LL-F28249 compounds, or nemadectins (Carter et al, 1988). The structures of the major nemadectins (the term used henceforth) are shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…(a) Structures of the major nemadectins produced by S541. Nemadectins 3, 1, 2 and 4 are, respectively, compounds LL-F28249a, fl, 1, and y (Carter et al, 1988). R1 = CH3 for nemadectin factors 1 and 4, C2H5 for factor 2 and (CH3)CH for factor 3.…”

Section: Introductionmentioning

confidence: 99%

Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide

Thomas

Cove

Baumberg

et al. 1991

Journal of General Microbiology

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Transformation of the thermotolerant streptomycete, soil isolate S541, with plasmid cloning vectors of varying size, copy number, and parent replicon (derived from pIJlO1, SCP2* and SLP1.2) depressed the biosynthesis of nemadectins (polyketide-derived secondary metabolites possessing anthelmintic activity). However, production of the chemically distinct 21-hydroxyl-oligomycin A, also produced by S541, was either unaffected or increased in plasmid-containing strains. A causal relationship between plasmid carriage and the changes in secondary metabolite yield was confirmed since cured strains were restored to normal production levels and their subsequent retransformation by plasmid DNA was followed by the same effects on nemadectin and oligomycin biosynthesis as before. All the plasmids tested were highly unstable in S541 and it was generally necessary to include an appropriate selective antibiotic (usually thiostrepton) in the growth medium. Thiostrepton was not responsible for the depressive effect, since this was also observed in plasmid-containing strains (i) when grown in antibiotic-free media and (ii) when alternative selective antibiotics such as neomycin were used. In addition, the plasmid-free strain produced both nemadectins and 21-hydroxyl-oligomycin A in the presence of sub-inhibitory levels of thiostrepton. The thiostrepton resistance gene, which was present on many of the plasmids tested, did not mediate the effect since plasmids carrying other selectable markers (pIJ58, neomycin, and pIJ355, viomycin) also depressed nemadectin but not 21-hydroxyl-oligomycin A production. No obvious recombination or integration events between S541 chromosomal DNA and any of the plasmids tested were revealed by DNA-DNA Southern hybridization.

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“…The correlations of H-35, H-36 and H-33 in the 1 H-1 H COSY spectrum and the HMBC correlations between H-35, H-36 and C-32, and between H-34, C-31 and C-32 connected the remaining six carbons as the 4-methyl-2-pentenyl moiety by analogy with the structure of nemadectin. 13,14 The correlation from H-34 to C-25 in the HMBC spectrum supported the linkage of the 4-methyl-2-pentenyl moiety with C-25 by C-31. Thus, the gross structure of compound 1 was established.…”

Section: Introductionmentioning

confidence: 79%

“…11,12 RESULTS AND DISCUSSION Isolation and structural elucidation Using bioactivity-guided separation of the components in the methanol extract of S. microflavus neau3 fermentation broth, compound 1 was afforded by twice silica gel column chromatography and semipreparative HPLC. The two seco-milbemycins from the S. bingchenggensis, analogous of compound 1, were obtained using the same approach, demonstrating that the two new seco-milbemycins and corresponding milbemycin b 14 were not converted to each other during purification by silica gel column and storage in MeOH extract at room temperature. 11 Compound 1 was isolated as colorless oil.…”

Section: Introductionmentioning

confidence: 80%

New nemadectin congener from Streptomyces microflavus neau3: fermentation, isolation, structure elucidation and biological activities

Xiang

Wang

et al. 2010

J Antibiot

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Bioactivity-guided fractionation of Streptomyces microflavus neau3 fermentation broth was used to determine the chemical identity of bioactive constituents. The structure of the new compound 1 was determined on the basis of spectroscopic analysis, including 1D and 2D NMR, as well as HRESI-MS, ESI-MS, UV and IR, and compared with the data reported in the literature. The acaricidal and nematocidal activities of the isolated compound 1 and its previously reported analogs 2, 3, 4 and 5 were evaluated. The results demonstrate that compounds 1, 2, 3, 4 and 5, especially compound 1, have potential as antiparasitics with acaricidal and nematocidal activities. These lactones shed new insights into the structural diversity of nemadectin and milbemycin analog libraries that are potentially accessible by combinatorial biosynthesis.

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LL-F28249 antibiotic complex: A new family of antiparastic macrocyclic lactones. Isolation, characterization and structures of LL-F28249 .ALPHA., .BETA., .GAMMA., .LAMBDA..

Cited by 66 publications

References 4 publications

Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity

Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity

Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide

New nemadectin congener from Streptomyces microflavus neau3: fermentation, isolation, structure elucidation and biological activities

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