Condensation-independent intramodular translocation mechanism of the trans-AT polyketide synthase assembly line.

A condensation-independent transacylation mechanism in trans-AT PKSs enables intramodular polyketide chain translocation without decarboxylation, involving KS 0 acting as a transacylase.

• Why it matters: Understanding how nonelongating modules facilitate chain translocation without decarboxylation fills a key gap in knowledge about polyketide biosynthesis and enzyme efficiency, which is crucial for bioengineering.
• What they did: The study used structural modeling and site-directed mutagenesis to reveal a conserved KS 0 -ACP binding mode across diverse modules, demonstrating KS 0’s role as a transacylase and highlighting the importance of ACP recycling.
• The result: These insights clarify the evolutionary adaptation and domain crosstalk in trans-AT PKSs, enabling improved polyketide synthesis strategies and advancing potential engineering of biosynthetic pathways.