Revealthe biobase cyanogramide biosynthesis pathways and new mechanisms of the source of marine linebacteria.

Recently, the international journal Angewandte Chemie International Edition (German Applied Chemistry) published online a research paper by Zhang Changsheng, a researcher at the South China Sea Ocean Institute of the Chinese Academy of Sciences, and Zhu Weiming, a professor at The University of The Ataline of China. Spirooxindole Formation Catalyzed by a P450 Enzyme", revealing the recombination activation of the biobase cyanogramide biosynthesis pathway from the source of marine line bacteria and the new mechanism for P450 oxidase to catalyze the formation of the oxidizing zircon ring.
alkaloid cyanogramide (1) isolated from ocean-sourced rare line-breaking bacteria Actinoallotichus cyanogriseus WH1-2216-6, containing the rare oxidizing snails of sic mitar .1,2-c The prosthesis structure effectively reverses tumor cell line resistance, such as adriamycin resistance cell strains K562/A02, MCF-7/Adr and vincristine resistant cell strains KB/VCR.
very low yield of 1 of the wild strains, limiting its broader bioactivity assessment and in-depth development. the research on biosynthesis of
microbial secondary metabolites is an effective way to discover novel synthesis mechanism, increase yield and increase structural diversity.
researchers reconstructed a biosynthetic gene cluster of 1 in the heterogenous host Streptomyces Coelicolor YF11, successfully realizing the heterogenous expression of 1, and the yield of 1 was significantly improved compared to wild type.
at the same time, nine structural analogues were identified from the heterogeneous expression bacteria, including five new compounds cyanogramide B-D (4-6), marinacarlinesbo E-F (3,8). further research
found that compound 4 is an exosome, compound 5, 6 and 1 is a mixture of heterogeneous bodies, the ratio is 5a/5b is 4:1, 6a/6b is 5:1, 1a/1b is 8:1, of which 6a absolute configuration is determined by single crystal diffraction to 12S.
the biosynthesis pathways of cyanogramide were clarified through systematic gene deletion, secondary metabolic intermediate isolation identification and precursor feeding experiments.
the zirconiator-oxidizing ring structure unit is widely found in natural products and is an important pharmaceutical-active group in active compounds, but its biosynthesis mechanism has only been reported in fungi.
has reported two kinds of anti-oxidant screw-ring catalytic mechanism, one is through the epoxy intermediate, by the semi-frequency which alcohol re-emission reaction produced, by the progesterone, the other is produced through free radicals, by P450 oxidase catalysis.
researchers found that, unlike the fungus 450 oxidase that produces oxidizing pyridoxine rings through a free radical mechanism, the oxidizing pyridine screw ring in compound 1 is formed by a semi-frequency alcohol rearrangement (Figure 2) by P450, mediated by carbon positive ions.
discovery of this new mechanism expands the understanding of the catalytic function of P450 oxidase. Zhu Yiguang, a researcher at the South China Sea Ocean Institute of
, and Zhang Qingbo, an associate researcher, are the co-first authors of the paper, and the research work has been supported by the opening of the Qingdao National Laboratory for Marine Science and Technology Pilot, the National Natural Science Foundation project, the National Key Research and Development Program project and the strategic pilot science and technology project of the Chinese Academy of Sciences.
Source: South China Sea Institute of Oceanography.