Unprecedented Noncanonical Features of the Nonlinear Nonribosomal Peptide Synthetase Assembly Line for WS9326A Biosynthesis
Unprecedented Noncanonical Features of the Nonlinear Nonribosomal Peptide Synthetase Assembly Line for WS9326A Biosynthesis
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DOI：
10.1002/anie.202103872
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发表时间：
2021-06-17
影响因子：
16.6
通讯作者：
Yoon, Yeo Joon
中科院分区：
文献类型：
--
作者：
Kim, Myoun-Su;Bae, Munhyung;Yoon, Yeo Joon
非核糖体肽合成酶（NRPS）结构域的系统失活和硫酯酶（TE）结构域的易位揭示了几个前所未有的非线性NRPS组装过程中的环缩肽WS 9326 A在链霉菌SNM 55的生物合成。首先，两组Iota Iota TE（TE Iota Iota）样酶介导活化氨基酸在两组独立腺苷酸化（A）-硫醇化（T）双结构域模块和具有独特特异性和灵活性的“无A”缩合（C）-T模块之间的穿梭。这通过A-T双结构域对TE及其结构的亲和力的阐明得到证实。第二，C-T双结构域模块迭代地且独立于同一蛋白质中的其他模块操作以催化两个链延伸循环。第三，这种生物合成途径包括模块跳跃的第一个例子，其中插入的C和T结构域是链转移所必需的。
Systematic inactivation of nonribosomal peptide synthetase (NRPS) domains and translocation of the thioesterase (TE) domain revealed several unprecedented nonlinear NRPS assembly processes during the biosynthesis of the cyclodepsipeptide WS9326A in Streptomyces sp. SNM55. First, two sets of type Iota Iota TE (TE Iota Iota)-like enzymes mediate the shuttling of activated amino acids between two sets of stand-alone adenylation (A)-thiolation (T) didomain modules and an "A-less" condensation (C)-T module with distinctive specificities and flexibilities. This was confirmed by the elucidation of the affinities of the A-T didomains for the TE Iota Iota s and its structure. Second, the C-T didomain module operates iteratively and independently from other modules in the same protein to catalyze two chain elongation cycles. Third, this biosynthetic pathway includes the first example of module skipping, where the interpolated C and T domains are required for chain transfer.