Structure and biosynthesis of fumosorinone, a new protein tyrosine phosphatase 1B inhibitor firstly isolated from the entomogenous fungus Isaria fumosorosea
| Autor: | Chengshu Wang, Chuan Chen, Lin-Xia Liu, Jun Zhang, Jitao Teng, Du-Qiang Luo |
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| Rok vydání: | 2015 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Magnetic Resonance Spectroscopy Pyridones Molecular Sequence Data Hydroxamic Acids Microbiology Gene Knockout Techniques Inhibitory Concentration 50 Polyketide chemistry.chemical_compound Biosynthesis Transcription (biology) Gene cluster Genetics Enzyme Inhibitors DNA Fungal Gene Regulator gene Protein Tyrosine Phosphatase Non-Receptor Type 1 Molecular Structure biology Sequence Analysis DNA biology.organism_classification Biosynthetic Pathways Insulin receptor Biochemistry chemistry Multigene Family Hypocreales biology.protein Isaria fumosorosea |
| Zdroj: | Fungal Genetics and Biology. 81:191-200 |
| ISSN: | 1087-1845 |
| DOI: | 10.1016/j.fgb.2015.03.009 |
| Popis: | Fumosorinone, isolated from the entomogenous fungus Isaria fumosorosea, is a new 2-pyridone alkaloid which is elucidated by HRESIMS 1D and 2DNMR. Fumosorinone is structurally similar to tenellin and desmethylbassianin but it differs in chain length and degree of methylation. It is characterized by a classic noncompetitive inhibitor of protein tyrosine phosphatase 1B (IC50 14.04 μM) which was implicated as a negative regulator of insulin receptor signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. For further study, we identified the biosynthetic gene cluster of fumosorinone from ongoing genome sequencing project, and it was verified by a direct knock-out strategy, reported for the first time in I. fumosorosea, using the Agrobacterium-mediated transformation in conjunction with linear deletion cassettes. The biosynthetic gene cluster includes a hybrid polyketide synthase–nonribosomal peptide synthetase gene, two cytochrome P450 enzyme genes, a trans-enoyl reductase gene, and other two transcription regulatory genes. Comparison of fumosorinone biosynthetic cluster with known gene clusters gives further insight into biosynthesis of pyridone alkaloids and provides the foundation for combinatorial biosynthesis for new fumosorinone derivatives. |
| Databáze: | OpenAIRE |
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