Targeted Rediscovery and Biosynthesis of the Farnesyl‐Transferase Inhibitor Pepticinnamin E
Targeted Rediscovery and Biosynthesis of the Farnesyl‐Transferase Inhibitor Pepticinnamin E
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法呢基转移酶抑制剂胃蛋白酶 E 的靶向重新发现和生物合成
DOI：
10.1002/cbic.201900025
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发表时间：
2019
期刊：
影响因子：
3.2
通讯作者：
Li, Bo
中科院分区：
文献类型：
--
作者：
Santa Maria, Kevin C.;Chan, Andrew N.;O'Neill, Erinn M.;Li, Bo
The natural product pepticinnamin E potently inhibits protein farnesyl transferases and has potential applications in treating cancer and malaria. Pepticinnamin E contains a rare N‐terminal cinnamoyl moiety as well as several nonproteinogenic amino acids, including the unusual 2‐chloro‐3‐hydroxy‐4‐methoxy‐N‐methyl‐L‐phenylalanine. The biosynthesis of pepticinnamin E has remained uncharacterized because its original producing strain is no longer available. Here we identified a gene cluster (pcm) for this natural product in a new producer,Actinobacteria bacteriumOK006, by means of a targeted rediscovery strategy. We demonstrated that thepcmcluster is responsible for the biosynthesis of pepticinnamin E, a nonribosomal peptide/polyketide hybrid. We also characterized a keyO‐methyltransferase that modifies 3,4‐dihydroxy‐l‐phenylalanine. Our work has identified the gene cluster for pepticinnamins for the first time and sets the stage for elucidating the unique chemistry required for biosynthesis.
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从胃蛋白酶 E 文库中鉴定蛋白质法尼基转移酶的单底物和双底物抑制剂以及细胞凋亡诱导剂。
影响因子：
3.5
作者：
Michael Thutewohl;L. Kissau;Boriana Popkirova;Ionna;T. Nowak;Michael Bate;J. Kuhlmann;O. Müller;H. Waldmann
通讯作者：
H. Waldmann
影响因子：
64.8
作者：
Haslinger, Kristina;Peschke, Madeleine;Cryle, Max J.
通讯作者：
Cryle, Max J.
影响因子：
4
作者：
Uhlmann, Stefanie;Suessmuth, Roderich D.;Cryle, Max J.
通讯作者：
Cryle, Max J.
影响因子：
4.4
作者：
Nelson, James T.;Lee, Jaeheon;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.
胃蛋白酶 E 文库的固相合成。
影响因子：
3.5
作者：
Michael Thutewohl;H. Waldmann
通讯作者：
H. Waldmann