Fig. 1: Splitting BusA into smaller, separately translated PKS subunits improves biosynthetic efficiency.

a The Modular polyketide synthases (mPKSs) for butenyl-spinosyn and salinomycin. The modules in each mPKS protein are joined with linkers. The modules between mPKS proteins are organised by docking domains to form a megasynthase complex. The operons in the butenyl-spinosyn, and salinomycin PKS gene cluster are indicated with arrows. CDDSlnA1, the C-terminal docking domain of the salinomycin PKS SlnA1. NDDSlnA2, the N-terminal docking domain of the salinomycin PKS SlnA2. CDDSlnA7, the C-terminal docking domain of the salinomycin PKS SlnA7. NDDSlnA8, the N-terminal docking domain of the salinomycin PKS SlnA8. TGA, stop codon. ATG, start codon. RBS, ribosomal binding site. b The three strategies used to split BusA. The linkers between the two modules were removed and replaced with exogenous docking domains from two adjacent salinomycin mPKSs. c Butenyl-spinosyn production by S. albus J1074 strains harbouring gene clusters containing wild-type busA (2.36 mg L−1) or split busA indicated in (b). n = 3 independent fermentation samples. Data are presented as the mean ± S.D. The p-values of the two-tailed t test are indicated. Source data are provided as a Source Data file.