ArticleACS catalysis2025
Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System.
Article in ACS catalysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Development of Keystone Macrolide Antibiotics via Selective Oxidation.ACS central science · 2026Article
- Article
- Directed Evolution of a Macrolide-Sensing Transcription Factor Biosensor for the Detection of Macrolactone Aglycones via "Effector Walking" and Efflux Pump Deletion.Biochemistry · 2025Article
- Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation.ACS catalysis · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
Modular type I polyketide synthases (PKSs) comprise a family of enzymes that synthesize a diverse class of natural products with medicinal applications. The biochemical features of these systems include the extension and processing of polyketide chains in a stepwise, stereospecific manner, organized by a series of modules divided into distinct catalytic domains. Previous work revealed that a primary hurdle for utilizing PKS modules to create diverse macrolactones hinges on the selectivity of the thioesterase (TE) domain. Herein, we generated novel hybrid 12-membered macrolactone/lactam ring systems employing unnatural amide-containing hexaketide intermediates in conjunction with an engineered TE S148C mutant from the pikromycin (Pik) biosynthetic pathway. Specifically, unnatural macrocycle (
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