Unique post-translational oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from Streptomyces sp. FXJ1.264.
Unique post-translational oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from Streptomyces sp. FXJ1.264.
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链霉菌新型核糖体肽的唑霉素复合物生物合成中独特的翻译后肟形成。
DOI：
10.1039/c5sc03021h
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发表时间：
2016-01-01
期刊：
影响因子：
8.4
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Liu N;Song L;Liu M;Shang F;Anderson Z;Fox DJ;Challis GL;Huang Y
黄素依赖性单加氧酶AzmF在新型核糖体肽天然产物的阿唑霉素复合物的生物合成过程中催化翻译后肟的形成。链霉菌是生物活性特化代谢物的丰富来源，包括快速增长的核糖体生物合成和后修饰肽（RiPP）天然产物的几个例子。本文报道了从链霉菌FXJ1.264中发现的唑霉素A-D，一种新的含有唑的线性肽的复合物，它含有一个独特的肟官能团。链霉菌FXJ1.264基因组草图序列的生物信息学分析鉴定了一组基因，假设这些基因负责从核糖体生物合成的前体中制备唑霉素。该簇内基因的失活消除了唑来霉素的产生，与这一假设一致。此外，缺乏azmE和azmF基因的突变体分别积累了缺乏O-甲基和氨基取代N-末端肟的唑来霉素衍生物（以及蛋白水解衍生物）。因此，AzmE，一种假定的S-腺苷甲硫氨酸依赖性甲基转移酶，负责唑来霉素生物合成中的后期O-甲基化反应，AzmF，一种假定的黄素依赖性单加氧酶，催化唑来霉素前体中的N-末端氨基氧化为相应的肟。据我们所知，肟形成是RiPP生物合成中迄今未知的翻译后修饰。
The flavin-dependent monooxygenase AzmF catalyses posttranslational oxime formation during biosynthesis of the azolemycin complex of novel ribosomal peptide natural products. Streptomycetes are a rich source of bioactive specialized metabolites, including several examples of the rapidly growing class of ribosomally-biosynthesized and post-translationally-modified peptide (RiPP) natural products. Here we report the discovery from Streptomyces sp. FXJ1.264 of azolemycins A–D, a complex of novel linear azole-containing peptides incorporating a unique oxime functional group. Bioinformatics analysis of the Streptomyces sp. FXJ1.264 draft genome sequence identified a cluster of genes that was hypothesized to be responsible for elaboration of the azolemycins from a ribosomally-biosynthesized precursor. Inactivation of genes within this cluster abolished azolemycin production, consistent with this hypothesis. Moreover, mutants lacking the azmE and azmF genes accumulated azolemycin derivatives lacking the O-methyl groups and an amino group in place of the N-terminal oxime (as well as proteolysed derivatives), respectively. Thus AzmE, a putative S-adenosyl methionine-dependent methyl transferase, is responsible for late-stage O-methylation reactions in azolemycin biosynthesis and AzmF, a putative flavin-dependent monooxygenase, catalyzes oxidation of the N-terminal amino group in an azolemycin precursor to the corresponding oxime. To the best of our knowledge, oxime formation is a hitherto unknown posttranslational modification in RiPP biosynthesis.
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影响因子：
2.9
作者：
Melby, Joel O.;Li, Xiangpo;Mitchell, Douglas A.
通讯作者：
Mitchell, Douglas A.
影响因子：
4
作者：
Deane, Caitlin D.;Melby, Joel O.;Molohon, Katie J.;Susarrey, Aziz R.;Mitchell, Douglas A.
通讯作者：
Mitchell, Douglas A.
DOI：
10.1073/pnas.1307111110
发表时间：
2013-05-21
影响因子：
11.1
作者：
Malcolmson, Steven J.;Young, Travis S.;Walsh, Christopher T.
通讯作者：
Walsh, Christopher T.
影响因子：
15
作者：
Lodewyk, Michael W.;Soldi, Cristian;Tantillo, Dean J.
通讯作者：
Tantillo, Dean J.
DOI：
10.1039/c39750000121
发表时间：
1975-01-01
影响因子：
--
作者：
BYCROFT, BW;PINCHIN, R
通讯作者：
PINCHIN, R