Distinct roles of tandem acyl carrier protein domains in the assembly of a macrocyclic polylactone

Abstract

Mutagenesis of the tandem acyl carrier protein (ACP₁–ACP₂) domains in the non-reducing polyketide synthase Men2 revealed their distinct roles in menisporopsin A biosynthesis. ACP₁ is essential for multiple esterifications and cyclolactonisation, whilst ACP₂ assembles the aromatic subunits of menisporopsin A. These findings provide a foundation for engineering macrocyclic polylactone compounds.