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Angew Chem Int Ed Engl. 2018 Dec 21;57(52):17009-17013. doi: 10.1002/anie.201806865. Epub 2018 Nov 27.

Trapping the Complex Molecular Machinery of Polyketide and Fatty Acid Synthases with Tunable Silylcyanohydrin Crosslinkers.

Author information

1
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.

Abstract

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.

KEYWORDS:

biosynthesis; natural products; protein crosslinking; protein labeling; synthases

PMID:
30379389
PMCID:
PMC6407627
[Available on 2019-12-21]
DOI:
10.1002/anie.201806865
[Indexed for MEDLINE]

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