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A Defined and Flexible Pocket Explains Aryl Substrate Promiscuity of the Cahuitamycin Starter Unit–Activating Enzyme CahJ
Author(s) -
Tripathi Ashootosh,
Park Sung Ryeol,
Sikkema Andrew P.,
Cho Hyo Je,
Wu Jianfeng,
Lee Brian,
Xi Chuanwu,
Smith Janet L.,
Sherman David H.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800233
Subject(s) - nonribosomal peptide , enzyme , peptide , aryl , stereochemistry , chemistry , substrate (aquarium) , biochemistry , combinatorial chemistry , biosynthesis , biology , organic chemistry , ecology , alkyl
Cahuitamycins are biofilm inhibitors assembled by a convergent nonribosomal peptide synthetase pathway. Previous genetic analysis indicated that a discrete enzyme, CahJ, serves as a gatekeeper for cahuitamycin structural diversification. Here, the CahJ protein was probed structurally and functionally to guide the formation of new analogues by mutasynthetic studies. This analysis enabled the in vivo production of a new cahuitamycin congener through targeted precursor incorporation.