Isoprenoid (prenyl) diphosphate biosynthesis (IPP/DMAPP -> GPP -> FPP -> GGPP)

The isoprenoid-diphosphate trunk converts the universal five-carbon isoprene units produced by the mevalonate pathway (or, in bacteria and plastids, the MEP pathway; both curated separately) into the linear trans-prenyl diphosphates that seed the major downstream isoprenoid classes. Isopentenyl- diphosphate delta-isomerase (type 1 IDI) reversibly interconverts isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP), supplying the allylic primer. Farnesyl diphosphate synthase then carries out two sequential head-to-tail (trans, 1'-4) condensations: DMAPP + IPP -> geranyl diphosphate (GPP, C10), and GPP + IPP -> farnesyl diphosphate (FPP, C15). FPP is the central branch point: it feeds sterol synthesis (cholesterol in animals, ergosterol in fungi, via squalene), heme A, ubiquinone side chains, dolichol (cis-prenyltransferases) and protein farnesylation. A geranylgeranyl diphosphate synthase adds one more IPP to FPP giving geranylgeranyl diphosphate (GGPP, C20), the donor for protein geranylgeranylation. The GGPP step has two architectures: a dedicated homomeric GGPP synthase (human GGPS1, budding-yeast BTS1), or, in fission yeast, which lacks a GGPS1/BTS1 homolog, a heteromer of the FPP synthase Fps1 with an inactive FPP-synthase-like subunit Spo9. All enzymes are soluble Mg2+-dependent isomerases/prenyltransferases (animal IDI1/IDI2 also peroxisomal). The pathway is the pharmacological target of nitrogen bisphosphonates (FDPS); human GGPS1 loss-of-function causes a muscular dystrophy / sensorineural hearing loss / ovarian insufficiency syndrome.

MODULE:isoprenoid_diphosphate_biosynthesisDRAFTCONCRETEMetabolic Pathwaymodules/isoprenoid_diphosphate_biosynthesis.yaml
isoprenoid biosynthetic processGO:0008299 trans, trans-farnesyl diphosphate biosynthetic processGO:0045337 geranylgeranyl diphosphate biosynthetic processGO:0033386
GO:0008299
isoprenoid biosynthetic process
IDI, FPP synthase and GGPP synthase build the linear prenyl diphosphates of isoprenoid metabolism (GO:0008299).
GO:0045337
trans, trans-farnesyl diphosphate biosynthetic process
FPP synthase produces farnesyl diphosphate (GO:0045337) via GPP (GO:0033384).
GO:0033386
geranylgeranyl diphosphate biosynthetic process
GGPP synthase produces geranylgeranyl diphosphate (GO:0033386).
YeastPathways:PWY-5123
trans, trans-farnesyl diphosphate biosynthesis (S. cerevisiae, SGD YeastPathways)
YeastCyc lists IDI1 (IPP isomerase) and ERG20 (both the GPP- and FPP-forming condensations) for this frame; both assignments were retained. The frame stops at FPP; the GGPP synthase BTS1 was added from the literature (PMID:7665600). COQ1 (hexaprenyl diphosphate synthase) is a long-chain prenyltransferase of the ubiquinone pathway and is modelled with coenzyme Q biosynthesis, not here.
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae.
Purification of yeast IPP isomerase and isolation of its structural gene (IDI1).
Oligonucleotide probes based on the protein sequence were used to isolate the structural gene encoding IPP isomerase from a yeast lambda library.
PMID:2681213
Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae.
The yeast FPP synthase gene (ERG20) is essential and supplies C15 precursors for sterols, dolichols and ubiquinones.
demonstrates that the gene is an essential, single copy number gene in yeast.
PMID:7665600
BTS1 encodes a geranylgeranyl diphosphate synthase in Saccharomyces cerevisiae.
BTS1 is the budding-yeast GGPP synthase; it is not essential but is needed for normal protein geranylgeranylation.
This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase.
PMID:17596513
Geranylgeranyl diphosphate synthase in fission yeast is a heteromer of farnesyl diphosphate synthase (FPS), Fps1, and an FPS-like protein, Spo9, essential for sporulation.
In S. pombe, Fps1 is the FPP synthase, no GGPS homolog exists, and GGPP synthase activity requires a complex of Fps1 with the FPS-like Spo9.
Thus, neither Fps1 nor Spo9 alone functions as a GGPS, but the two proteins together form a complex with GGPS activity.
file:yeast/ERG10/ERG10-ai-review.yaml
ERG10 gene review (S. cerevisiae)
Upstream context only: ERG10 supplies acetoacetyl-CoA to the mevalonate pathway that produces the IPP consumed here.
PMID:41700894
Harnessing evolution: leveraging bacterial isoprenoid pathway diversity toward improved bioengineering strategies.
2026 review noting that IPP/DMAPP isomerase exists as two structurally unrelated types with different cofactor requirements. This module models only the type I (PTHR10885) enzyme, and human IDI2 is a type I paralog, not a type II enzyme.
It is the only shared enzyme between both the MEV and MEP pathways and is found in two forms that are structurally unrelated and have different cofactor requirements (36).
file:human/IDI1/IDI1-ai-review.yaml
IDI1 gene review (human)
IPP<->DMAPP isomerase, ubiquitous (UniProtKB:Q13907, GO:0004452) matches the completed human IDI1 review.
file:human/IDI2/IDI2-ai-review.yaml
IDI2 gene review (human)
IPP<->DMAPP isomerase, muscle-enriched paralog (UniProtKB:Q9BXS1, GO:0004452) matches the completed human IDI2 review.
file:human/FDPS/FDPS-ai-review.yaml
FDPS gene review (human)
Farnesyl diphosphate synthase, DMAPP+IPP->GPP->FPP (UniProtKB:P14324, GO:0004337/GO:0004161) matches the completed human FDPS review.
file:human/GGPS1/GGPS1-ai-review.yaml
GGPS1 gene review (human)
Geranylgeranyl diphosphate synthase, FPP+IPP->GGPP (UniProtKB:O95749, GO:0004311) matches the completed human GGPS1 review.
6Nodes
3Parts
1Variant Sets
2Variants
4Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:isoprenoid_diphosphate_biosynthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • ipp_isomerization → fpp_synthesis [NOT_CHECKED]
  • fpp_synthesis → ggpp_synthesis [NOT_CHECKED]

Function consistency and core coverage

9 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (13 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
idi_activity IDI1 (human; ubiquitous)
UniProtKB:Q13907
Family Representative 		isopentenyl-diphosphate delta-isomerase activity
GO:0004452 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
idi_activity IDI2 (human; muscle-enriched)
UniProtKB:Q9BXS1
Family Representative 		isopentenyl-diphosphate delta-isomerase activity
GO:0004452 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
idi_activity IDI1 (Saccharomyces cerevisiae)
UniProtKB:P15496
Family Representative 		isopentenyl-diphosphate delta-isomerase activity
GO:0004452 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
idi_activity idi1 (Schizosaccharomyces pombe)
UniProtKB:Q10132
Family Representative 		isopentenyl-diphosphate delta-isomerase activity
GO:0004452 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fdps_activity FDPS (human)
UniProtKB:P14324
Family Representative 		(2E,6E)-farnesyl diphosphate synthase activity
GO:0004337 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fdps_activity ERG20 (Saccharomyces cerevisiae)
UniProtKB:P08524
Family Representative 		(2E,6E)-farnesyl diphosphate synthase activity
GO:0004337 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fdps_activity fps1 (Schizosaccharomyces pombe)
UniProtKB:O14230
Family Representative 		(2E,6E)-farnesyl diphosphate synthase activity
GO:0004337 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ggps1_activity GGPS1 (human)
UniProtKB:O95749
Family Representative 		geranylgeranyl diphosphate synthase activity
GO:0004311 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ggps1_activity BTS1 (Saccharomyces cerevisiae)
UniProtKB:Q12051
Family Representative 		geranylgeranyl diphosphate synthase activity
GO:0004311 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fps1_spo9_ggps_activity PROTEIN_COMPLEX
Gene 		geranylgeranyl diphosphate synthase activity
GO:0004311 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
idi_activity IDI / isopentenyl-diphosphate delta-isomerase (type 1) family
PANTHER:PTHR10885
Family 		isopentenyl-diphosphate delta-isomerase activity
GO:0004452 		Family Supported
Family review supports GO:0004452 FAMILY_WIDE. Asserted by isoprenoid_diphosphate_biosynthesis; accepted by IDI1 (S. cerevisiae, S. pombe, human) and IDI2.
fdps_activity FDPS / farnesyl pyrophosphate synthase family
PANTHER:PTHR11525
Family 		(2E,6E)-farnesyl diphosphate synthase activity
GO:0004337 		Family Supported
Family review supports GO:0004337 FAMILY_WIDE. Asserted by isoprenoid_diphosphate_biosynthesis; accepted by ERG20, fps1 and FDPS. spo9 is a member exception.
ggps1_activity GGPS1 / geranylgeranyl pyrophosphate synthase family
PANTHER:PTHR12001:SF44
Family 		geranylgeranyl diphosphate synthase activity
GO:0004311 		Family Supported
Family review supports GO:0004311 for PANTHER:PTHR12001:SF44. GGPS (SF44), as isoprenoid_diphosphate_biosynthesis asserts on the base family.

Gene-review completeness (10/10 grounded genes reviewed)

9 complete review(s) · 3 with deep research · 0 missing review · 7 reviewed but lacking deep research

Gene Review Complete Deep research
BTS1 Q12051 ✓ ✓ ✓
ERG20 P08524 ✓ 42/43 ✓
FDPS P14324 ✓ ✓ ✗
fps1 O14230 ✓ ✓ ✗
GGPS1 O95749 ✓ ✓ ✗
IDI1 P15496 ✓ ✓ ✓
idi1 Q10132 ✓ ✓ ✗
IDI1 Q13907 ✓ ✓ ✗
IDI2 Q9BXS1 ✓ ✓ ✗
spo9 O59703 ✓ ✓ ✗

Details

Context
cytosolGO:0005829 peroxisomeGO:0005777
Isoprenoid (prenyl) diphosphate biosynthesisMetabolic Pathwayisoprenoid_diphosphate_biosynthesis
isoprenoid biosynthetic processGO:0008299 trans, trans-farnesyl diphosphate biosynthetic processGO:0045337 geranylgeranyl diphosphate biosynthetic processGO:0033386
Context
cytosolGO:0005829 peroxisomeGO:0005777

Isoprenoid (prenyl) diphosphate biosynthesis trunk (GO:0008299), the bridge between the mevalonate pathway (mevalonate_pathway) and the sterol (sterol_commitment_squalene_to_lanosterol, ergosterol_biosynthesis), dolichol, ubiquinone and protein-prenylation branches. Aligned to YeastCyc PWY-5123 and the PomBase isoprenoid GO-CAM: S. cerevisiae IDI1 (P15496) and ERG20 (P08524), S. pombe idi1 (Q10132) and fps1 (O14230) were added as representatives of the existing families, and BTS1 (Q12051; PTHR12001), which YeastCyc does not list in this frame, was added to the GGPP step. The GGPP step became a variant set, because fission yeast makes GGPP with a heteromer of the FPP synthase Fps1 and the FPS-like Spo9 instead of a GGPS1/BTS1 homolog (PMID:17596513). The PomBase GO-CAM types spo9 as an FPP synthase (GO:0004337) and does not model the heteromer's GGPS activity. Its UniProt name (geranylgeranyl pyrophosphate synthase) reflects the heteromer and should not be read as activity of Spo9 alone. COQ1 (hexaprenyl diphosphate synthase), mentioned in the crosswalk, belongs to coenzyme Q biosynthesis (YeastCyc HEXPPSYN-PWY-2) and is excluded; cis-prenyltransferases for dolichol (RER2/SRT1, S. pombe rer2) are also downstream branches. Human content kept: IDI1/IDI2 (cytosol + peroxisome via PTS1), FDPS (nitrogen-bisphosphonate target; partial reactions GO:0004161/GO:0004337 share one active site) and GGPS1 (homohexamer; loss-of-function -> muscular dystrophy/sensorineural hearing loss/ovarian insufficiency). Connections were retyped from PROVIDES_INPUT_FOR to PRECEDES. Scope note (2026 review PMID:41700894): the IDI step here is the type I, metal-dependent isomerase family (PTHR10885). The structurally unrelated type II IDI used by archaea and many bacteria is not modeled. Despite its name, human IDI2 is a type I paralog of IDI1 and not a type II enzyme.

Connections

IPP isomerase supplies the DMAPP primer (and balances IPP) that FPP synthase condenses to GPP/FPP.
FPP made by FPP synthase is the substrate GGPP synthase elongates to GGPP.
Part 1: IPP/DMAPP isomerization
Isopentenyl-diphosphate delta-isomerase (type 1 IDI)Reactionipp_isomerization

Annotons

isopentenyl-diphosphate delta-isomerase (type 1)
idi_activity
Participant: Family: IDI / isopentenyl-diphosphate delta-isomerase (type 1) family
Family:
IDI / isopentenyl-diphosphate delta-isomerase (type 1) familyPANTHER:PTHR10885
Representative Members: IDI1 (human; ubiquitous)UniProtKB:Q13907 IDI2 (human; muscle-enriched)UniProtKB:Q9BXS1 IDI1 (Saccharomyces cerevisiae)UniProtKB:P15496 idi1 (Schizosaccharomyces pombe)UniProtKB:Q10132

Function

isopentenyl-diphosphate delta-isomerase activityGO:0004452
Substrates: isopentenyl diphosphate (IPP)
Products: dimethylallyl diphosphate (DMAPP)

Locations

cytosolGO:0005829 peroxisomeGO:0005777

Interconvert IPP and DMAPP to supply the allylic primer and balance the isoprene-unit pools. The peroxisome location applies to the animal enzymes; the yeast enzymes are recorded as cytoplasmic.

Part 2: GPP + FPP synthesis (trans-prenyltransferase)
Farnesyl diphosphate synthase (FDPS / ERG20 / Fps1)Reactionfpp_synthesis

Annotons

farnesyl diphosphate synthase (DMAPP+IPP->GPP->FPP)
fdps_activity
Participant: Family: FDPS / farnesyl pyrophosphate synthase family
Family:
FDPS / farnesyl pyrophosphate synthase familyPANTHER:PTHR11525
Representative Members: FDPS (human)UniProtKB:P14324 ERG20 (Saccharomyces cerevisiae)UniProtKB:P08524 fps1 (Schizosaccharomyces pombe)UniProtKB:O14230

Function

(2E,6E)-farnesyl diphosphate synthase activityGO:0004337
Substrates: dimethylallyl diphosphate (DMAPP) isopentenyl diphosphate (IPP; Mg2+)
Products: (2E,6E)-farnesyl diphosphate (FPP) geranyl diphosphate (GPP; intermediate) diphosphate

Locations

cytosolGO:0005829

Elongate DMAPP with two IPP units to the C15 branch-point precursor FPP.

Part 3: GGPP synthesis (trans-prenyltransferase)
Geranylgeranyl diphosphate synthase (FPP + IPP -> GGPP)Reactionggpp_synthesis
Variant set: GGPP synthase architecture by enzyme architecture (Exactly One)
Dedicated homomeric GGPP synthase (GGPS1 / BTS1)Reactionhomomeric_ggps_variant

Annotons

geranylgeranyl diphosphate synthase (FPP+IPP->GGPP)
ggps1_activity
Participant: Family: GGPS1 / geranylgeranyl pyrophosphate synthase family
Family:
GGPS1 / geranylgeranyl pyrophosphate synthase family
Representative Members: GGPS1 (human)UniProtKB:O95749 BTS1 (Saccharomyces cerevisiae)UniProtKB:Q12051

Function

geranylgeranyl diphosphate synthase activityGO:0004311
Substrates: (2E,6E)-farnesyl diphosphate (FPP) isopentenyl diphosphate (IPP; Mg2+)
Products: (2E,6E,10E)-geranylgeranyl diphosphate (GGPP) diphosphate

Locations

cytosolGO:0005829

Elongate FPP with one IPP unit to the C20 donor GGPP.

Heteromeric FPS / FPS-like GGPP synthase (S. pombe Fps1-Spo9)Protein Complexfps_heteromer_ggps_variant

S. pombe has no GGPS1/BTS1-family protein. GGPP synthase activity appears only when Fps1 and the FPS-like Spo9 are co-expressed, the two proteins interact, and spo9 mutants have reduced GGPS activity and impaired geranylgeranylation (PMID:17596513). Spo9 alone does not complement an FPS-deficient budding-yeast mutant. Both proteins belong to the FPP synthase family PTHR11525.

Annotons

Fps1-Spo9 heteromeric geranylgeranyl diphosphate synthase
fps1_spo9_ggps_activity
Participant: Protein Complex: Fps1-Spo9 GGPP synthase heteromer
Protein Complex:
Fps1-Spo9 GGPP synthase heteromer Complex of the catalytic FPP synthase Fps1 and the FPS-like Spo9 subunit; the complex, not either subunit, has GGPS activity.
Active units:
Fps1 catalytic FPP synthase subunit
Participant: Gene Product: fps1 (Schizosaccharomyces pombe)
Gene Product:
fps1 (Schizosaccharomyces pombe)UniProtKB:O14230
Role: FPP synthase that, together with Spo9, forms the GGPP-synthesising heteromer.
Spo9 FPS-like subunit
Participant: Gene Product: spo9 (Schizosaccharomyces pombe)
Gene Product:
spo9 (Schizosaccharomyces pombe)UniProtKB:O59703
Role: FPS-like partner required for GGPS activity of the heteromer; lacks FPS activity on its own.

Function

geranylgeranyl diphosphate synthase activityGO:0004311
Substrates: (2E,6E)-farnesyl diphosphate (FPP) isopentenyl diphosphate (IPP)
Products: (2E,6E,10E)-geranylgeranyl diphosphate (GGPP)

Locations

cytosolGO:0005829

Fission-yeast route to GGPP in the absence of a dedicated GGPS; required for geranylgeranylation of proteins needed for forespore-membrane expansion.