Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis.
Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis.
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DOI：
10.1038/s41467-023-38484-8
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发表时间：
2023-05-17
影响因子：
16.6
通讯作者：
Tang, Yi
中科院分区：
文献类型：
--
作者：
Jenner, Matthew;Hai, Yang;Nguyen, Hong H.;Passmore, Munro;Skyrud, Will;Kim, Junyong;Garg, Neil K.;Zhang, Wenjun;Loo, Rachel R. Ogorzalek R.;Tang, Yi
铁载体属于铁色素家族，是真菌物种生存所必需的，并且对许多病原真菌的毒力起关键作用。尽管它们的生物学意义，我们的理解，这些铁螯合环状hexapeptides是如何组装的非核糖体肽合成酶（NRPS）酶仍然知之甚少，主要是由于非线性表现出的域架构。在这里，我们报告的生物化学表征的SidC NRPS，负责建设的细胞内铁载体铁微菌素。纯化的SidC的体外重建揭示了其产生ferricrocin及其结构变体ferrichrome的能力。完整蛋白质质谱的应用揭示了肽基铁载体生物合成过程中的几个非典型事件，包括氨基酸底物的模块间加载和能够形成聚酰胺键的腺苷酸化结构域。这项工作扩大了NRPS编程的范围，允许生物合成的铁色素NRPS分配，并设置了新的异羟肟酸支架的重编程阶段。真菌铁载体是由非核糖体肽合成酶（NRPS）生物合成的，具有非常不寻常的结构域结构。在这里，作者解释了SidC NRPS内发生的神秘编程事件，负责构巢曲霉中的铁微菌素生物合成。
Siderophores belonging to the ferrichrome family are essential for the viability of fungal species and play a key role for virulence of numerous pathogenic fungi. Despite their biological significance, our understanding of how these iron-chelating cyclic hexapeptides are assembled by non-ribosomal peptide synthetase (NRPS) enzymes remains poorly understood, primarily due to the nonlinearity exhibited by the domain architecture. Herein, we report the biochemical characterization of the SidC NRPS, responsible for construction of the intracellular siderophore ferricrocin. In vitro reconstitution of purified SidC reveals its ability to produce ferricrocin and its structural variant, ferrichrome. Application of intact protein mass spectrometry uncovers several non-canonical events during peptidyl siderophore biosynthesis, including inter-modular loading of amino acid substrates and an adenylation domain capable of poly-amide bond formation. This work expands the scope of NRPS programming, allows biosynthetic assignment of ferrichrome NRPSs, and sets the stage for reprogramming towards novel hydroxamate scaffolds. Fungal siderophores are biosynthesised by nonribosomal peptide synthetases (NRPSs) with highly unusual domain architectures. Here, the authors characterise cryptic programming events occurring within SidC NRPS, responsible for ferricrocin biosynthesis in Aspergillus nidulans.
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影响因子：
14.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
Brandenburger, Eileen;Gressler, Markus;Hoffmeister, Dirk
通讯作者：
Hoffmeister, Dirk
影响因子：
3.8
作者：
Koulman A;Lee TV;Fraser K;Johnson L;Arcus V;Lott JS;Rasmussen S;Lane G
通讯作者：
Lane G
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.5
作者：
DEML, G;VOGES, K;WINKELMANN, G
通讯作者：
WINKELMANN, G