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Trapping the Complex Molecular Machinery of Polyketide and Fatty Acid Synthases with Tunable Silylcyanohydrin Crosslinkers
Author(s) -
Konno Sho,
La Clair James J.,
Burkart Michael D.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201806865
Subject(s) - polyketide , acyl carrier protein , chemistry , trapping , mechanism (biology) , computational biology , enzyme , combinatorial chemistry , nanotechnology , biochemistry , stereochemistry , biology , materials science , biosynthesis , physics , ecology , quantum mechanics
Many families of natural products are synthesized by large multidomain biological machines commonly referred to as megasynthases. While the advance of mechanism‐based tools has opened new windows into the structural features within the protein–protein interfaces guiding carrier protein dependent enzymes, there is an immediate need for tools that can be engaged to link co‐translated domains in a site‐selective manner. Now, the use of silylcyanohydrins is demonstrated in a two‐step, two‐site selective crosslinking for the trapping of carrier–protein interactions within megasynthases. This advance provides a new tool to trap intermediate states within multimodular systems, a key step toward understanding the specificities within fatty acid (FAS) and polyketide (PKS) synthases.