Fabclavine biosynthesis in X. szentirmaii: shortened derivatives and characterization of the thioester reductase FclG and the condensation domain-like protein FclL
Fabclavine biosynthesis in X. szentirmaii: shortened derivatives and characterization of the thioester reductase FclG and the condensation domain-like protein FclL
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DOI：
10.1007/s10295-018-02124-8
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Bode, Helge B.
中科院分区：
文献类型：
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作者：
Wenski, Sebastian L.;Kolbert, Diana;Bode, Helge B.
Fabclavines是一种不常见的肽-聚酮-多胺杂合体，对革兰氏阳性菌、革兰氏阴性菌、真菌和原生动物具有广谱的生物活性。我们阐明了这些NRPS-PKS杂合体的生物合成在Xabhabdus szentirmaii通过删除大部分基因编码的蚕豆碱BGC和随后的分析产生的蚕豆碱或多胺中间体。因此，我们确定了缩短的fabclavines类似于生物活性的玉米胺。此外，我们详细分析了硫酯还原酶FclG和独立的缩合结构域样蛋白FclL，并观察到这两种酶的低底物特异性。
Fabclavines, unusual peptide-polyketide-polyamine hybrids, show broad-spectrum bioactivity against a variety of different organism like Gram-positive and -negative bacteria, fungi and protozoa. We elucidated the biosynthesis of these NRPS-PKS hybrids in Xenorhabdus szentirmaii by deletion of most genes encoded in the fabclavine BGC and subsequent analysis of produced fabclavine or polyamine intermediates. Thereby, we identified shortened fabclavines similar to the bioactive zeamines. Furthermore, we analyzed the thioester reductase FclG and the free-standing condensation domain-like protein FclL in detail and observed low substrate specificity for both enzymes.