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

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.

SUBMITTER: Konno S

PROVIDER: S-EPMC6407627 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Konno Sho S La Clair James J JJ Burkart Michael D MD

Angewandte Chemie (International ed. in English) 20181127 52

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 selec ...[more]

PMID: 30379389

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