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

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.