Dictyostelium DIF-1 (differentiation-inducing factor 1) biosynthesis

Biosynthesis of DIF-1, the chlorinated polyketide morphogen that induces prestalk/stalk cell differentiation in the social amoeba Dictyostelium discoideum. The pathway builds and tailors a hexanoyl-primed acylphloroglucinol in three enzymatic stages: (1) the hybrid type I/type III "steely" polyketide synthase StlB condenses a hexanoyl-CoA starter with malonyl-CoA extender units to make the acylphloroglucinol backbone THPH (1-(3,5-dihydroxy-... phloro- caprophenone); (2) the flavin-dependent halogenase ChlA chlorinates THPH, first to 3-chloro-THPH and then to 3,5-dichloro-THPH (des-methyl-DIF-1); and (3) the O-methyltransferase DmtA methylates des-methyl-DIF-1 to yield mature DIF-1. DIF-1 is then secreted and read out by the prestalk transcriptional machinery (DimA/DimB). This module is Dictyostelium-specific but phrased over enzyme functions and family selectors with D. discoideum representative members rather than a fixed gene list, so a related steely-PKS / halogenase / O-MT route in another dictyostelid could be substituted. OUT OF SCOPE: the DIF-1 RESPONSE (DimA/DimB-driven prestalk/prespore patterning; a separate module), DIF-1 dechlorination/inactivation (the DIF catabolic arm), and the additional O-methylation intermediates upstream of chlorination — only the three named, reviewed enzymes StlB, ChlA and DmtA are grounded here.

Dictyostelium-specific secondary-metabolite/morphogen module grounded to the three reviewed enzymes StlB (Q54FI3, GO:0106265), ChlA (Q54FI4, GO:0140907) and DmtA (Q8T638, GO:0106268). GO molecular-function terms were taken from the completed DICDI gene reviews; each step uses a PANTHER family selector (generic over orthologs) plus the concrete D. discoideum representative member. The canonical pathway also includes O-methylation intermediates between the StlB product and the ChlA chlorination steps; these are noted but not separately grounded here because only StlB, ChlA and DmtA are experimentally characterised and reviewed. Named to signal Dictyostelium scope so it does not collide with a generic reusable polyketide/secondary-metabolite module.