Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex.
Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex.
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通过 COM 结构域介导的普利他汀 NRPS 复合物重编程生物组合合成新型脂肽
DOI：
10.3389/fmicb.2016.01801
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发表时间：
2016
影响因子：
5.2
通讯作者：
Bie X
中科院分区：
文献类型：
--
作者：
Liu H;Gao L;Han J;Ma Z;Lu Z;Dai C;Zhang C;Bie X
通讯介导 (COM) 结构域的供体和受体对于协调非核糖体肽合成酶 (NRPS) 复合物内的分子间通讯至关重要。不同的 COM 结构域组提供选择性，允许 NRPS 利用不同的天然生物合成模板。在这项研究中，通过重新编程普利司他汀生物合成机制来合成新型脂肽。 Thr-to-Asp 点突变足以将 ppsB 供体 COM 结构域的选择性转向 ppsD。删除和/或互换性建立了供体和受体功能。受体COM结构域的变化在其伙伴供体存在的情况下不会导致新产物的形成，而普利他汀的形成通过改变供体模块而完全消除。通过高分辨率 LC-ESI-MS/MS 鉴定并验证了五种新型脂肽（环状五肽、线性六肽、九肽、七肽和环状八肽）。此外，我们证明了通过选择相容的 COM 结构域来生成具有抗菌活性的新型菌株的潜力，并且新型脂肽在浓度为 31.25–125 μg/ml 时对 5 种真菌表现出抗菌活性。
Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD. Deletion and/or interchangeability established donor and acceptor function. Variations in acceptor COM domain did not result in novel product formation in the presence of its partner donor, whereas plipastatin formation was completely abrogated by altering donor modules. Five novel lipopeptides (cyclic pentapeptide, linear hexapeptide, nonapeptide, heptapeptide, and cyclic octapeptide) were identified and verified by high-resolution LC-ESI-MS/MS. In addition, we demonstrated the potential to generate novel strains with the antimicrobial activity by selecting compatible COM domains, and the novel lipopeptides exhibited antimicrobial activity against five of the fungal species at a contention of 31.25–125 μg/ml.
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影响因子：
2.2
作者：
Deng, Yang;Lu, Zhaoxin;Bie, Xiaomei
通讯作者：
Bie, Xiaomei
影响因子：
3.8
作者：
Hiradate, S;Yoshida, S;Fujii, Y
通讯作者：
Fujii, Y
影响因子：
2.9
作者：
Eppelmann, K;Stachelhaus, T;Marahiel, MA
通讯作者：
Marahiel, MA
DOI：
10.1073/pnas.172226299
发表时间：
2002-08-20
影响因子：
11.1
作者：
Chin, JW;Martin, AB;Schultz, PG
通讯作者：
Schultz, PG
影响因子：
6.7
作者：
Guo, Qinggang;Dong, Weixin;Ma, Ping
通讯作者：
Ma, Ping