Bioactive gibberellin (GA4/GA1) biosynthesis from geranylgeranyl diphosphate

Biosynthesis of the bioactive gibberellins GA4 and GA1 in vascular plants from the plastid diterpene precursor (E,E,E)-geranylgeranyl diphosphate (GGPP), decomposed into three compartment-defined stages that use three enzyme classes. (1) In the plastid stroma two terpene cyclases make the tetracyclic hydrocarbon ent-kaurene: the class II cyclase ent-copalyl diphosphate synthase (CPS) converts GGPP to ent-copalyl diphosphate (the first committed step) and the class I cyclase ent-kaurene synthase (KS) converts ent-CPP to ent-kaurene with release of diphosphate. (2) Two multifunctional cytochrome P450 monooxygenases at the plastid envelope and endoplasmic reticulum oxidize ent-kaurene to GA12: ent-kaurene oxidase (KO, CYP701A) performs three oxidations of C-19 to give ent-kaurenoic acid, and ent-kaurenoic acid oxidase (KAO, CYP88A) performs three further oxidations, including B-ring contraction, to give GA12, the first gibberellin. (3) Soluble 2-oxoglutarate/Fe(II)-dependent dioxygenases in the cytosol complete the pathway: GA 20-oxidase (GA20ox) oxidizes and removes C-20 of GA12 (via GA15 and GA24) to give the C19 gibberellin GA9, and GA 3-oxidase (GA3ox) 3beta-hydroxylates GA9 to bioactive GA4. The same two dioxygenases act on the 13-hydroxylated series (GA53 to GA20 to GA1). The early stages are encoded by single or few genes, whereas GA20ox and GA3ox are multigene families whose transcription is the main point of control of bioactive GA levels (feedback repression through DELLA signaling, light and developmental regulation). GGPP supply, GA 13-hydroxylation, GA 2-oxidase and other deactivation routes, GA transport, and GA perception/DELLA signaling are outside this module's boundary.

Arabidopsis thaliana members are used as representative members (all have completed gene reviews under genes/ARATH/: GA1, GA2, GA3, KAO1, KAO2, GA20OX1, GA3OX1); the module itself is phrased taxon-neutrally for vascular plants. Annoton molecular functions match the gene reviews' core_functions. PANTHER subfamily ids were checked against interpro/panther/panther.obo; no PANTHER id is asserted for KAO (KAO1 and KAO2 fall in different PTHR24286 subfamilies) or for GA20ox/GA3ox (UniProt maps them only to the broad 2OG-Fe(II) oxygenase superfamily PTHR47990). Paralogs not reviewed here (GA20ox2-5, GA3ox2-4) contribute the same activities in a tissue- and stage-specific manner. GA 2-oxidases (C19- and C20-GA 2-oxidases), which deactivate GA4/GA1 and their precursors, are context for homeostasis rather than parts of this biosynthetic module. No production GO-CAM in gocams/index.tsv contains these Arabidopsis gene products.