Figure 2 - D. discoideum type III PKSs occur as C-terminal domains of steely FAS-PKS hybrids.

(a) Active site and signature sequence comparison of steely type III PKSs with plant and bacterial type III PKSs (Medicago sativa (alfalfa) CHS and Streptomyces coelicolor 1,3,6,8-tetrahydroxynaphthalene synthase, THNS) and related type II (plant and bacterial) FAS enzymes (Arabidopsis thaliana and E. coli KAS III enzymes). Signature sequences are highlighted in yellow or blue, red marks the conserved catalytic triad, and green indicates type III PKS specificity-determining positions. Numbering is for alfalfa CHS2. (b) Predicted enzymatic domains of D. discoideum steely proteins, including N-terminal type I FAS-PKS and C-terminal type III PKS domains. Type I FAS-PKS intermediates are tethered by a thioester linkage to either a KS cysteine or the prosthetic Ppant arm of the ACP-like domain. AA (amino acid) labels indicate the total number of residues in each steely protein or the amino acid position of intron boundaries. (c) Proposed PCP biosynthesis by a steely FAS I–PKS III hybrid. Direct transfer of a hexanoyl intermediate to the type III PKS domain based on analogous off loading of conventional type I FAS-PKS products via activity of thioesterase (TE) domains (Supplementary Fig. 1).