Discovery of Antimycin-Type Depsipeptides from a wbl Gene Mutant Strain of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production

Abstract

Deepsea microbes are a rich source of novel bioactive compounds, which have developed unique genetic systems as well as biosynthetic pathways compared with those of terrestrial microbes in order to survive in extreme living environment. However, a large variety of deepsea-microbial secondary metabolic pathways remain “cryptic” under the normal laboratory conditions. Manipulation of global regulators is one of the effective approaches for triggering the production of cryptic secondary metabolites. In this study, by combination of various chromatographic purification process, we obtained somalimycin (1), a new antimycin-type depsipeptide, with an unusual substitution of 3-aminosalicylate instead of conserved 3-formamidosalicylate moiety, along with two known (2 and 3) analogs from the ΔwblAso mutant strain of deepsea-derived Streptomyces somaliensis SCSIO ZH66. The structures of 1–3 were elucidated on the basis of extensive spectroscopic analyses including LC-MS and NMR. In the evaluation of potent anti-inflammatory activity, compound 2 exhibited strong inhibitory activity on the IL-5 production in ovalbumin-stimulated splenocytes with IC50 value of 0.57 μM, while 1 and 3 displayed mild effect (>10 μM), which might be attributed to their different side-chain substitutions. Moreover, compounds 1–3 showed very weak cytotoxicity against human umbilical vein endothelial cells with LD50 values of 62.6, 34.6, and 192.9 μM, respectively, which were far over their IL-5 inhibitory activity. These results indicated that these compounds have good potential for further use in anti-inflammatory drug development.

Bioprospecting Deep-Sea Actinobacteria for Novel Anti-infective Natural Products

“…1 H and 13 C NMR analyses were also performed; the data are summarized in Table 3 and Supplementary Figures S2 , S3 . We found the spectroscopic results were identical to those of the known compound urauchimycin D which was also recently isolated from a deep-sea bacterium Streptomyces somaliensis SCSIO ZH66 ( Yao et al, 2006 ; Li et al, 2017 ). Hence, compound 1 was identified as urauchimycin D, one of well-known antifungal antimycins.…”

Extreme environments: microbiology leading to specialized metabolites

“…Inactivation of wblA 50 and vioB from a cold deep‐sea‐derived Streptomyces somaliensis strain led to spectacular changes in the production of specialized metabolites (Fig. ), notably in the synthesis of the new antimycin‐type depsipeptide, somalimycin ( 94 ) and two analogues, USF‐19A and urauchimycin D ( 95 , 96 ) (Li et al ). Chemical investigation of Marinactinospora thermotolerans, Streptomyces scopuliridis and Streptomyces drozdowiczii strains recovered from deep‐sea samples collected off South China (3865 m) led to the isolation of the cyclic peptides, marthiapeptide A ( 97 ), desotamide ( 98 ), desotamide B‐D ( 99 – 101 ) and marfomycins A–F ( 102 – 107 ) all of which showed antimicrobial activity against pathogenic Gram‐positive bacteria (Zhou et al , ; Song et al ).…”

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…[218]; a new N-acyl dopamine glycoside myxillin A (202) isolated from the Icelandic hydrothermal vent-derived sponge Myxilla incrustans [219]; the known steroidal saponin pectinioside A (203) isolated from the starfish Patiria pectinifera [220]; a new benzophenone polyketide peniphenone (204) obtained from the mangrove Sonneratia apetala endophytic fungus Penicillium sp. ZJ-SY 2 [221]; and a known analog of the antimycin-type depsipeptide somalimycin, named USF-19A (205) isolated from the South China Sea deep (3536 m) sediment-derived Streptomyces somaliensis SCSIO ZH66 [222].…”

“…As shown in Table 2 and Figure 2, in 2016-2017, the preclinical nervous system pharmacology of marine compounds (206)(207)(208)(209)(210)(211)(212)(213)(214)(215)(216)(217)(218)(219)(220)(221)(222)(223)(224)(225) reported several mechanisms of action involving potassium (K + ) channels, nicotinic acetylcholine, calcium (Ca 2+ ) and serotonin receptors, as well as in vivo models of antinociception and neuroprotection.…”