IB-96212, a Novel Cytotoxic Macrolide Produced by a Marine Micromonospora. I. Taxonomy, Fermentation, Isolation and Biological Activities.

Abstract

A novel bioactive macrolide, IB-96212 has been isolated from the fermentation broth of a marine actinomycete, L-25-ES25-008. The strain belongs to the genus Micromonospora. The macrolide showed a very strong cytotoxic activity against P-388, and lower but significant activity against A-549, HT-29, and MEL-28 cell lines. We describe the isolation, taxonomy and fermentation of the producing strain as well as the isolation ofIB-96212.A marine Micromonospora has been isolated from homogenates of a sponge. The strain has been found to produce a fermentation broth with cytotoxic activity. A new macrolide responsible for this activity has been isolated from this fermentation broth. Wedescribe in this paper the taxonomical characterization of the strain, its fermentation and the isolation of the active compound, together with the study of the in vitro activities. The structural elucidation is presented in an accompanyingpaper1}. Materials and Methods Mi cro organi sms

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

“…The bioactivities of compounds 1-4 were examined in antimicrobial and cytotoxicity assays ( [29,30] and TMC95A-D from an ascomycetous fungus Apiospora montagnei [31]; the (E)-2,3-dehydroadipyl appendage in compound 2 is unprecedented in natural products, only to see its (Z)-isomer in a siderophore of Mycobacterium avium [32]; the side chain on the spiroacetal rings in compounds 2-4 lack hydroxylation at C-31, which is the common modification shared with all oligomycin class antibiotics (oligomycin [33], dunaimycins [34], rutamycins [35], ossamycin [36], neomaclafungins [37], and IB-96212 [38]) and related polyketides with ring-truncation (ushikulides [39], yokonolides [40,41], A59770A [42], dunaimycins [34]) or expansion (neaumycins [43]) ( Figure 8). All these compounds, except for maclafungin [44], the producer of which was not identified, are metabolites of Streptomyces [33][34][35][36] or conventional rare actinomycetes [37,38]. Thus, a novel skeleton and new congeners with distinct structural features were discovered from an underexplored actinomycete of the genus Pseudosporangium, which was chosen with the aid of a database survey on the history of chemical studies and the presence of biosynthetic genes.…”

Secondary Metabolites from Marine Micromonospora: Chemistry and Bioactivities

“…The structure consists of a 26‐membered macrolide aglycone and an l ‐rhodinose sugar . Compound 9 presented very strong cytotoxic effect against lymphoma cell P388 (IC 50 =0.0001 μg/mL) and a potent cytotoxicity against human lung adenocarcinoma (A549), colon cancer (HT‐29), and human skin cancer (SK‐MEL‐28) cell lines with IC 50 values of 1 μg/mL …”

Actinomycetes: A General Review

“…Actinomycetes are known to play a role in mineralization of nutrients and organic matter decomposition, they are known to be lignocellulose decomposers [79]. They also acts as biocontrol agents, especially on cellulose containing organisms such as Phytophthora [80].…”