Discovery and Biosynthesis of Bolagladins: Unusual Lipodepsipeptides from Burkholderia gladioli Clinical Isolates*.
Discovery and Biosynthesis of Bolagladins: Unusual Lipodepsipeptides from Burkholderia gladioli Clinical Isolates*.
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DOI：
10.1002/anie.202009110
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发表时间：
2020-11-23
期刊：
影响因子：
--
通讯作者：
Challis GL
中科院分区：
文献类型：
--
作者：
Dashti Y;Nakou IT;Mullins AJ;Webster G;Jian X;Mahenthiralingam E;Challis GL
发现从囊性纤维化患者的肺中分离的两种唐菖蒲伯克霍尔德菌菌株产生含有独特的柠檬酸盐衍生脂肪酸和罕见的β-丙氨酸残基的不寻常的脂缩肽。通过生物信息学和插入突变技术，鉴定了其生物合成的基因簇。使用框内缺失和酶活性测定来研究由生物合成基因簇编码的几种蛋白质的功能，该基因簇存在于约45%的B.唐菖蒲分离物的基因组中，表明其代谢产物在该物种的生长和/或存活中起重要作用。 Chrome Azurol S试验表明，这些代谢产物与三价铁结合，当添加到生长培养基中时，三价铁抑制其产生。 此外，编码TonB依赖性铁载体受体的基因与生物合成基因相邻，表明这些代谢物可能在唐菖蒲B中起铁载体的作用。 Bolagladins A和B是从囊性纤维化患者的肺中分离的两种唐菖蒲伯克霍尔德菌菌株中发现的一种隐蔽的非核糖体肽合成酶的产物。 这些代谢产物含有独特的柠檬酸盐引发脂肪酸和罕见的β-丙氨酸残基。结合生物信息学分析和遗传和生化实验阐明了这些不寻常的结构特征的安装机制。
Two Burkholderia gladioli strains isolated from the lungs of cystic fibrosis patients were found to produce unusual lipodepsipeptides containing a unique citrate‐derived fatty acid and a rare dehydro‐β‐alanine residue. The gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In‐frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of about 45 % of B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S assay indicated that these metabolites bind ferric iron, which suppresses their production when added to the growth medium. Moreover, a gene encoding a TonB‐dependent ferric‐siderophore receptor is adjacent to the biosynthetic genes, suggesting that these metabolites may function as siderophores in B. gladioli. Bolagladins A and B were discovered as products of a cryptic nonribosomal peptide synthetase in two Burkholderia gladioli strains isolated from the lungs of cystic fibrosis patients. These metabolites contain a unique citrate‐primed fatty acid and a rare dehydro‐β‐alanine residue. A combination of bioinformatics analysis and genetic and biochemical experiments illuminated the mechanisms for the installation of these unusual structural features.
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伯克霍尔德氏菌基因组对非核糖体肽合成酶的挖掘揭示了新型铁载体和脂肽合成的巨大潜力。
影响因子：
3.4
作者：
Esmaeel Q;Pupin M;Kieu NP;Chataigné G;Béchet M;Deravel J;Krier F;Höfte M;Jacques P;Leclère V
通讯作者：
Leclère V
影响因子：
--
作者：
Cheung, Johnson;Murphy, Michael E. P.;Heinrichs, David E.
通讯作者：
Heinrichs, David E.
影响因子：
4.3
作者：
Franke, Jakob;Ishida, Keishi;Hertweck, Christian
通讯作者：
Hertweck, Christian
影响因子：
14.8
作者：
Ferreras, JA;Ryu, JS;Quadri, LEN
通讯作者：
Quadri, LEN
DOI：
10.1002/anie.202009107
发表时间：
2020-11-23
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Dose B;Ross C;Niehs SP;Scherlach K;Bauer JP;Hertweck C
通讯作者：
Hertweck C