Type-II (dissociated) fatty-acid synthesis, bacterial and mitochondrial

A reusable dissociated fatty-acid synthase (FAS II) pathway in which each reaction is catalysed by a separate enzyme acting on acyl chains carried by a free acyl carrier protein (ACP). Malonyl-CoA formed by acetyl-CoA carboxylase is loaded onto ACP, an acyl-ACP chain is initiated, and the chain is iteratively elongated through condensation, beta-keto reduction, dehydration, and enoyl reduction. The same architecture operates in bacteria (and plastids) and, as a conserved, endosymbiont-derived system, in the mitochondrial matrix of eukaryotes, where it is independent of the cytosolic type I FAS and its best-defined product is octanoyl-ACP, the precursor of lipoic acid. Mitochondrial FAS II uses a homomeric multidomain acetyl-CoA carboxylase, a mitochondrial ACP and partly unrelated reductase and dehydratase families. An optional FabA/FabB branch introduces and extends cis unsaturation in bacteria. Enzyme-family, cofactor and compartment variants are represented explicitly rather than collapsed into a type-I fatty-acid synthase.

MODULE:type_ii_fatty_acid_synthesisDRAFTMetabolic Pathwaymodules/type_ii_fatty_acid_synthesis.yaml

fatty acid biosynthetic processGO:0006633

YeastPathways:FASYN-ELONG2-PWY

fatty acid elongation (S. cerevisiae, SGD YeastPathways)

YeastCyc frame for the generic ACP-based elongation round, assigned to cytosolic FAS1/FAS2 mixed with the mitochondrial FAS II enzymes CEM1 (3-oxoacyl-ACP synthase) and OAR1 (3-oxoacyl-ACP reductase). The mitochondrial dehydratase HTD2, enoyl reductase ETR1, MCT1 and ACP1 are not listed. Mapped here to the mitochondrial FAS II variant; the FAS1/FAS2 parts belong to fatty_acid_de_novo_synthesis.

PMID:19028688

Mitochondrial fatty acid synthesis type II: more than just fatty acids.

Eukaryotes have a conserved mitochondrial FAS pathway independent of cytosolic FAS, catalysed by soluble enzymes resembling the prokaryotic system; octanoic acid is the direct precursor of lipoic acid, and yeast mutants are respiratory deficient with low lipoic acid.

PMID:16246072

Mitochondrial fatty acid synthesis and maintenance of respiratory competent mitochondria in yeast.

Characterisation of Etr1p, the HTD2/YHR067w dehydratase and Hfa1p as the mitochondrial acetyl-CoA carboxylase completed the yeast mitochondrial FAS II pathway.

PMID:14761959

HFA1 encoding an organelle-specific acetyl-CoA carboxylase controls mitochondrial fatty acid synthesis in Saccharomyces cerevisiae.

HFA1 encodes a mitochondrially targeted acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and lipoic acid synthesis; hfa1 mutants resemble mitochondrial FAS mutants.

PMID:9388293

Two genes of the putative mitochondrial fatty acid synthase in the genome of Saccharomyces cerevisiae.

OAR1 (YKL055c, 3-oxoacyl-ACP reductase homologue) and MCT1 (YOR221c, malonyl-CoA:ACP transferase homologue) disruptions are respiratory deficient, like the mitochondrial ACP and beta-ketoacyl-ACP synthase mutants.

PMID:8412701

Identification of a new nuclear gene (CEM1) encoding a protein homologous to a beta-keto-acyl synthase which is essential for mitochondrial respiration in Saccharomyces cerevisiae.

CEM1 encodes a beta-ketoacyl synthase homologue required for respiration but not for bulk fatty acid synthesis.

PMID:15387819

Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essential for mitochondrial function and morphology.

YHR067w/HTD2 encodes the mitochondrial 3-hydroxyacyl-thioester dehydratase 2 of mitochondrial FAS.

PMID:11509667

Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1'p), 2-enoyl thioester reductases essential for mitochondrial respiratory competence.

Ybr026p/ETR1 is a mitochondrial 2-enoyl thioester reductase required for respiration; the deletion is complemented by mitochondrially targeted E. coli FabI.

PMID:9187370

Mitochondrial acyl carrier protein is involved in lipoic acid synthesis in Saccharomyces cerevisiae.

acp1 deletion mutants retain only 5-10% of wild-type lipoic acid and are respiratory deficient.

PMID:18059524

Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.

ACP is a universal carrier of acyl intermediates in fatty acid synthesis.

GO:0006633

fatty acid biosynthetic process

GO:0006633 provides the biological-process scope for de novo fatty-acid chain initiation and elongation.

UniProtKB:P0A6Q3

Reviewed Escherichia coli FabA UniProt record

The reviewed E. coli FabA record has direct GO evidence for both FabA reactions and classifies the protein in PTHR30272:SF8.

UniProtKB:P0A953

Reviewed Escherichia coli FabB UniProt record

The reviewed E. coli FabB record has direct GO evidence for 3-oxoacyl-ACP synthase activity and classifies the protein in PTHR11712:SF306.

UniProtKB:P0AAI5

Reviewed Escherichia coli FabF UniProt record

The reviewed E. coli FabF record has direct GO evidence for 3-oxoacyl-ACP synthase activity and classifies the protein in PTHR11712:SF336.

file:modules/type_ii_fatty_acid_synthesis-deep-research-openscientist.md

OpenScientist research for the reusable type-II fatty-acid synthesis module

The module-level review supports the obligatory initiation and four-reaction elongation sequence, while documenting enzyme-family variation and the conditional FabA/FabB unsaturation branch.

file:projects/P_PUTIDA/deep-research/PSEPK__type_ii_fatty_acid_synthesis__ppu00061-deep-research-openscientist.md

OpenScientist PSEPK ppu00061 pathway satisfiability review

The species-aware review finds the KT2440 pathway satisfiable, identifies AcpP and FabV as core members, and flags several same-family paralogs as candidates that must not be assumed to perform the core pathway role.

file:PSEPK/accC/accC-ai-review.yaml

PSEPK accC gene review

The KT2440 review identifies Q88QD6 as the biotin-carboxylase subunit of acetyl-CoA carboxylase.

file:PSEPK/fabD/fabD-uniprot.txt

UniProtKB entry Q88LL7 for PSEPK FabD

UniProt identifies Q88LL7 as malonyl-CoA:ACP transacylase.

file:PSEPK/PP_4379/PP_4379-uniprot.txt

UniProtKB entry Q88ES4 for PSEPK PP_4379

UniProt assigns Q88ES4 beta-ketoacyl-ACP synthase III activity.

file:PSEPK/PP_4545/PP_4545-uniprot.txt

UniProtKB entry Q88EC1 for PSEPK PP_4545

UniProt assigns Q88EC1 beta-ketodecanoyl-ACP synthase activity.

file:PSEPK/PP_0262/PP_0262-uniprot.txt

UniProtKB entry Q88R72 for PSEPK PP_0262

UniProt links Q88R72 to the primary structural and biochemical study of the standalone MadB malonyl-ACP decarboxylase.

PMID:36796578

Initiation of fatty acid biosynthesis in Pseudomonas putida KT2440

Direct genetics and biochemistry establish three initiation routes: short-chain-acyl-CoA-selective FabH1, medium-chain-acyl-CoA-selective FabH2, and MadB-dependent production of acetyl-ACP from malonyl-ACP.

file:PSEPK/fabV/fabV-uniprot.txt

UniProtKB entry Q88E33 for PSEPK FabV

UniProt identifies Q88E33 as the NADH-dependent enoyl-ACP reductase of FAS-II.

33Nodes

14Parts

7Variant Sets

18Variants

22Annotons

11Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

type_ii_fatty_acid_synthesis-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

29 gene-function check(s) reflected in core functions · 0 conflict(s) · 19 evidence or coverage gap(s) (62 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.

Annoton	Participant	Function	Assessment
accABCD_complex	PROTEIN_COMPLEX Gene	acetyl-CoA carboxylase activity GO:0003989	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
accABCD_complex/accC_biotin_carboxylase	PSEPK AccC UniProtKB:Q88QD6 Family Representative	biotin carboxylase activity GO:0004075	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hfa1_mito_acc_activity	HFA1 (Saccharomyces cerevisiae) UniProtKB:P32874 Family Representative	acetyl-CoA carboxylase activity GO:0003989	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acpP_carrier	PSEPK AcpP UniProtKB:Q88LL5 Family Representative	acyl carrier activity GO:0000036	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acpP_carrier	ACP1 (Saccharomyces cerevisiae; mitochondrial) UniProtKB:P32463 Family Representative	acyl carrier activity GO:0000036	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acpP_carrier	SPAC4H3.09 (Schizosaccharomyces pombe; mitochondrial) UniProtKB:Q10217 Family Representative	acyl carrier activity GO:0000036	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabD_transacylase	PSEPK FabD UniProtKB:Q88LL7 Family Representative	acyl-carrier-protein S-malonyltransferase activity GO:0004314	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabD_transacylase	MCT1 (Saccharomyces cerevisiae; mitochondrial) UniProtKB:Q12283 Family Representative	acyl-carrier-protein S-malonyltransferase activity GO:0004314	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabD_transacylase	mct1 (Schizosaccharomyces pombe; mitochondrial) UniProtKB:O13698 Family Representative	acyl-carrier-protein S-malonyltransferase activity GO:0004314	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabH1_initiator	PSEPK FabH1 UniProtKB:Q88ES4 Family Representative	beta-ketoacyl-acyl-carrier-protein synthase III activity GO:0033818	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabH2_initiator	PSEPK FabH2 UniProtKB:Q88EC1 Family Representative	beta-ketodecanoyl-acyl-carrier-protein synthase activity GO:0061990	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mad_malonyl_acp_decarboxylase	PSEPK MadB UniProtKB:Q88R72 Family Representative	malonyl-ACP decarboxylase activity GO:0016831	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mad_route_kas_condensation	PSEPK FabB UniProtKB:Q88FC3 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mad_route_kas_condensation	PSEPK FabF UniProtKB:Q88LL4 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabB_condensing_activity	PSEPK FabB UniProtKB:Q88FC3 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabB_condensing_activity	experimentally characterized E. coli FabB UniProtKB:P0A953 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabF_condensing_activity	PSEPK FabF UniProtKB:Q88LL4 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabF_condensing_activity	experimentally characterized E. coli FabF UniProtKB:P0AAI5 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabF_condensing_activity	CEM1 (Saccharomyces cerevisiae; mitochondrial KAS) UniProtKB:P39525 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabF_condensing_activity	cem1 (Schizosaccharomyces pombe; mitochondrial KAS) UniProtKB:O94297 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabG_reductase	PSEPK FabG UniProtKB:Q88LL6 Family Representative	3-oxoacyl-acyl-carrier-protein reductase (NADPH) activity GO:0004316	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oar1_mito_reductase	OAR1 (Saccharomyces cerevisiae) UniProtKB:P35731 Family Representative	3-oxoacyl-acyl-carrier-protein reductase (NADPH) activity GO:0004316	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oar1_mito_reductase	oar2 (Schizosaccharomyces pombe) UniProtKB:O42866 Family Representative	3-oxoacyl-acyl-carrier-protein reductase (NADPH) activity GO:0004316	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabZ_dehydratase	PSEPK FabZ UniProtKB:Q88MG9 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabZ_dehydratase	experimentally characterized E. coli FabZ UniProtKB:P0A6Q6 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabA_dehydratase	PSEPK FabA UniProtKB:Q88FC4 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabA_dehydratase	experimentally characterized E. coli FabA UniProtKB:P0A6Q3 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
htd2_mito_dehydratase	HTD2 (Saccharomyces cerevisiae) UniProtKB:P38790 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
htd2_mito_dehydratase	htd2 (Schizosaccharomyces pombe) UniProtKB:Q9Y814 Family Representative	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabI_reductase	Escherichia coli FabI UniProtKB:P0AEK4 Family Representative	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabK_reductase	Streptococcus pneumoniae R6 FabK UniProtKB:Q8DR17 Family Representative	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabV_reductase	PSEPK FabV UniProtKB:Q88E33 Family Representative	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabL_reductase	Bacillus subtilis FabL UniProtKB:P71079 Family Representative	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
etr1_mito_reductase	ETR1 (Saccharomyces cerevisiae) UniProtKB:P38071 Family Representative	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etr1_mito_reductase	etr1 (Schizosaccharomyces pombe) UniProtKB:Q10488 Family Representative	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etr1_mito_reductase	MECR (human) UniProtKB:Q9BV79 Family Representative	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabA_isomerase	PSEPK FabA UniProtKB:Q88FC4 Family Representative	trans-2-decenoyl-acyl-carrier-protein isomerase activity GO:0034017	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabA_isomerase	experimentally characterized E. coli FabA UniProtKB:P0A6Q3 Family Representative	trans-2-decenoyl-acyl-carrier-protein isomerase activity GO:0034017	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fabB_unsaturated_branch	PSEPK FabB UniProtKB:Q88FC3 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fabB_unsaturated_branch	experimentally characterized E. coli FabB UniProtKB:P0A953 Family Representative	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
accC_biotin_carboxylase	bacterial AccC biotin carboxylases Family	biotin carboxylase activity GO:0004075	Family Id Missing The family has no identifier linking it to a curated family review.
hfa1_mito_acc_activity	eukaryotic multidomain acetyl-CoA carboxylase family (mitochondrial isoform) PANTHER:PTHR45728 Family	acetyl-CoA carboxylase activity GO:0003989	Family Supported Family review supports GO:0003989 FAMILY_WIDE. Asserted by fatty_acid_de_novo_synthesis and type_ii_fatty_acid_synthesis; accepted by every reviewed member.
acpP_carrier	FAS-II acyl carrier proteins (bacterial AcpP and mitochondrial ACP) PANTHER:PTHR20863 Family	acyl carrier activity GO:0000036	Family Supported Family review supports GO:0000036 FAMILY_WIDE. Asserted by type_ii_fatty_acid_synthesis; accepted by P. putida AcpP, ACP1 and SPAC4H3.09.
fabD_transacylase	FabD-like malonyl-CoA:ACP transacylases (bacterial and mitochondrial) Family	acyl-carrier-protein S-malonyltransferase activity GO:0004314	Family Id Missing The family has no identifier linking it to a curated family review.
fabH1_initiator	FabH-like beta-ketoacyl-ACP synthase III enzymes PANTHER:PTHR34069:SF2 Family	beta-ketoacyl-acyl-carrier-protein synthase III activity GO:0033818	Family Supported Family review supports GO:0033818 for PANTHER:PTHR34069:SF2. SF2 FabH enzymes, as type_ii_fatty_acid_synthesis asserts for P. putida FabH1. PqsC in SF2 is a secondary-metabolism homolog with a generic acyltransferase core.
fabH2_initiator	medium-chain-acyl-CoA-selective FabH enzymes PANTHER:PTHR34069:SF2 Family	beta-ketodecanoyl-acyl-carrier-protein synthase activity GO:0061990	Family Supported Family review supports GO:0061990 for PANTHER:PTHR34069:SF2. The medium-chain-selective P. putida FabH2 (PP_4545) in SF2.
mad_malonyl_acp_decarboxylase	Mad/YiiD-family malonyl-ACP decarboxylases Family	malonyl-ACP decarboxylase activity GO:0016831	Family Id Missing The family has no identifier linking it to a curated family review.
mad_route_kas_condensation	FabB/FabF elongation condensing enzymes PANTHER:PTHR11712 Family	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Family Function Unreviewed Family review leaves GO:0004315 UNRESOLVED. The inventory includes mitochondrial Cem1, bacterial and plastid fatty-acid ketosynthases, and aromatic polyketide synthase alpha and beta components. Experimental chain-length-factor work separates the noncatalytic beta component from the condensing enzyme (PMID:14558809). Thus even the shared ketosynthase architecture does not confer condensation chemistry on every member. Pombe Cem1 is an SF336 mitochondrial fatty-acid-synthesis comparison, not a polyketide antibiotic assignment.
fabB_condensing_activity	FabB/KAS-I condensing enzymes PANTHER:PTHR11712:SF306 Family	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Family Function Unreviewed Family review leaves GO:0004315 UNRESOLVED. The inventory includes mitochondrial Cem1, bacterial and plastid fatty-acid ketosynthases, and aromatic polyketide synthase alpha and beta components. Experimental chain-length-factor work separates the noncatalytic beta component from the condensing enzyme (PMID:14558809). Thus even the shared ketosynthase architecture does not confer condensation chemistry on every member. Pombe Cem1 is an SF336 mitochondrial fatty-acid-synthesis comparison, not a polyketide antibiotic assignment.
fabF_condensing_activity	FabF/KAS-II condensing enzymes PANTHER:PTHR11712:SF336 Family	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Family Function Unreviewed Family review leaves GO:0004315 UNRESOLVED. The inventory includes mitochondrial Cem1, bacterial and plastid fatty-acid ketosynthases, and aromatic polyketide synthase alpha and beta components. Experimental chain-length-factor work separates the noncatalytic beta component from the condensing enzyme (PMID:14558809). Thus even the shared ketosynthase architecture does not confer condensation chemistry on every member. Pombe Cem1 is an SF336 mitochondrial fatty-acid-synthesis comparison, not a polyketide antibiotic assignment.
fabG_reductase	FabG-family 3-oxoacyl-ACP reductases PANTHER:PTHR42879:SF2 Family	3-oxoacyl-acyl-carrier-protein reductase (NADPH) activity GO:0004316	Family Supported Family review supports GO:0004316 for PANTHER:PTHR42879:SF2. FabG within SF2, as type_ii_fatty_acid_synthesis asserts on the base family. SF2 also contains HbdH and HSDHs.
oar1_mito_reductase	fungal mitochondrial 3-oxoacyl-ACP reductases (SDR) PANTHER:PTHR42760:SF133 Family	3-oxoacyl-acyl-carrier-protein reductase (NADPH) activity GO:0004316	Family Supported Family review supports GO:0004316 for PANTHER:PTHR42760:SF133. FabG-like 3-oxoacyl-ACP reductase subfamilies, as type_ii_fatty_acid_synthesis selects SF133 for OAR1/oar2.
fabZ_dehydratase	FabZ-family FAS-II dehydratases PANTHER:PTHR30272:SF1 Family	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Family Supported Family review supports GO:0019171 FAMILY_WIDE. Asserted by bacterial_unsaturated_fatty_acid_biosynthesis and type_ii_fatty_acid_synthesis; accepted by P. putida FabZ and FabA.
fabA_dehydratase	FabA-family dehydratase/isomerases PANTHER:PTHR30272:SF8 Family	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Family Supported Family review supports GO:0019171 FAMILY_WIDE. Asserted by bacterial_unsaturated_fatty_acid_biosynthesis and type_ii_fatty_acid_synthesis; accepted by P. putida FabZ and FabA.
htd2_mito_dehydratase	fungal mitochondrial hydroxyacyl-thioester dehydratase type 2 PANTHER:PTHR28152 Family	(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activity GO:0019171	Family Supported Family review supports GO:0019171 FAMILY_WIDE. Asserted by type_ii_fatty_acid_synthesis; accepted by HTD2 and htd2.
fabI_reductase	FabI-family NADH-dependent enoyl-ACP reductases PANTHER:PTHR43159 Family	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Family Supported Family review supports GO:0004318 FAMILY_WIDE. Asserted by type_ii_fatty_acid_synthesis; PAINT root node PTN001215190, seeded by E. coli FabI, B. subtilis FabI, M. tuberculosis InhA and Arabidopsis MOD1.
fabK_reductase	FabK-family flavin-dependent enoyl-ACP reductases Family	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Family Id Missing The family has no identifier linking it to a curated family review.
fabV_reductase	NADH-dependent bacterial enoyl-ACP reductases PANTHER:PTHR37480:SF1 Family	enoyl-acyl-carrier-protein reductase (NADH) activity GO:0004318	Family Supported Family review supports GO:0004318 FAMILY_WIDE. Asserted by type_ii_fatty_acid_synthesis (SF1); accepted by P. putida FabV.
fabL_reductase	FabL-like NADPH-dependent enoyl-ACP reductases Family	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Family Id Missing The family has no identifier linking it to a curated family review.
etr1_mito_reductase	mitochondrial 2-enoyl thioester reductases (MDR superfamily) PANTHER:PTHR43981 Family	enoyl-acyl-carrier-protein reductase (NADPH) activity GO:0141148	Family Supported Family review supports GO:0141148 FAMILY_WIDE. Asserted by type_ii_fatty_acid_synthesis; accepted by ETR1 and etr1.
fabA_isomerase	FabA-family dehydratase/isomerases PANTHER:PTHR30272:SF8 Family	trans-2-decenoyl-acyl-carrier-protein isomerase activity GO:0034017	Family Supported Family review supports GO:0034017 for PANTHER:PTHR30272:SF8. FabA (SF8) only, as both modules select.
fabB_unsaturated_branch	FabB/KAS-I condensing enzymes PANTHER:PTHR11712:SF306 Family	3-oxoacyl-acyl-carrier-protein synthase activity GO:0004315	Family Function Unreviewed Family review leaves GO:0004315 UNRESOLVED. The inventory includes mitochondrial Cem1, bacterial and plastid fatty-acid ketosynthases, and aromatic polyketide synthase alpha and beta components. Experimental chain-length-factor work separates the noncatalytic beta component from the condensing enzyme (PMID:14558809). Thus even the shared ketosynthase architecture does not confer condensation chemistry on every member. Pombe Cem1 is an SF336 mitochondrial fatty-acid-synthesis comparison, not a polyketide antibiotic assignment.

Gene-review completeness (28/36 grounded genes reviewed)

28 complete review(s) · 23 with deep research · 8 missing review · 5 reviewed but lacking deep research

Gene	Review	Complete	Deep research
accA Q88MG4	✓	✓	✓
accB Q88QD5	✓	✓	✓
accC Q88QD6	✓	✓	✓
accD Q88LD9	✓	✓	✓
ACP1 P32463	✓	✓	✓
acpP Q88LL5	✓	✓	✓
cem1 O94297	✓	✓	✓
CEM1 P39525	✓	✓	✓
ETR1 P38071	✓	✓	✓
etr1 Q10488	✓	✓	✗
fabA Q88FC4	✓	✓	✓
fabB Q88FC3	✓	✓	✓
fabD Q88LL7	✓	✓	✓
fabF Q88LL4	✓	✓	✓
fabG Q88LL6	✓	✓	✓
fabV Q88E33	✓	✓	✓
fabZ Q88MG9	✓	✓	✓
HFA1 P32874	✓	✓	✓
HTD2 P38790	✓	✓	✓
htd2 Q9Y814	✓	✓	✗
mct1 O13698	✓	✓	✗
MCT1 Q12283	✓	✓	✓
OAR1 P35731	✓	✓	✓
oar2 O42866	✓	✓	✗
experimentally characterized E. coli FabA P0A6Q3	✗	—	—
experimentally characterized E. coli FabZ P0A6Q6	✗	—	—
experimentally characterized E. coli FabB P0A953	✗	—	—
experimentally characterized E. coli FabF P0AAI5	✗	—	—
Escherichia coli FabI P0AEK4	✗	—	—
Bacillus subtilis FabL P71079	✗	—	—
PP_0262 Q88R72	✓	✓	✓
PP_4379 Q88ES4	✓	✓	✓
PP_4545 Q88EC1	✓	✓	✓
Streptococcus pneumoniae R6 FabK Q8DR17	✗	—	—
MECR (human) Q9BV79	✗	—	—
SPAC4H3.09 Q10217	✓	✓	✗

Tree

Type-II fatty-acid synthesisMetabolic Pathwaytype_ii_fatty_acid_synthesis

Parts
1. 1. malonyl-CoA formation
2. Acetyl-CoA carboxylaseReactionacetyl_coa_carboxylation
  
  Variants
  1. Acetyl-CoA carboxylase architecture by enzyme architecture / compartment (Exactly One)
    
    Heteromeric bacterial AccABCD carboxylaseProtein Complexheteromeric_accabcd_variant
    
    Annotons
    
    Heteromeric acetyl-CoA carboxylase Protein Complex: bacterial AccABCD acetyl-CoA carboxylase
    
    Mitochondrial homomeric multidomain carboxylase (fungal HFA1)Reactionmitochondrial_homomeric_acc_variant
    
    Annotons
    
    HFA1: mitochondrial acetyl-CoA carboxylase Family: eukaryotic multidomain acetyl-CoA carboxylase family (mitochondrial isoform)
3. 2. acyl-group carriage
4. Acyl carrier proteinMolecular Functionacp_carrier_role
  
  Annotons
  - Holo-acyl carrier protein Family: FAS-II acyl carrier proteins (bacterial AcpP and mitochondrial ACP)
5. 3. malonyl-ACP formation
6. FabD malonyl-ACP loadingReactionmalonyl_acp_loading
  
  Annotons
  - Malonyl-CoA:ACP transacylase Family: FabD-like malonyl-CoA:ACP transacylases (bacterial and mitochondrial)
7. 4. fatty-acid chain initiation
8. Alternative FAS-II chain-initiation routesMetabolic Pathwaychain_initiation
  
  Variants
  1. Fatty-acid chain-initiation route by primer source and initiating enzyme chemistry (One Or More)
    
    KAS-III acyl-CoA-dependent initiationReactionkasIII_route
    
    Variants
    
    KAS-III acyl-CoA substrate variants by acyl-CoA primer range (One Or More)
    
    FabH1 short-chain-acyl-CoA initiationReactionfabH1_short_chain_variant
    
    Annotons
    
    FabH1 beta-ketoacyl-ACP synthase III Family: FabH-like beta-ketoacyl-ACP synthase III enzymes
    
    FabH2 medium-chain-acyl-CoA initiationReactionfabH2_medium_chain_variant
    
    Annotons
    
    FabH2 beta-ketodecanoyl-ACP synthase Family: medium-chain-acyl-CoA-selective FabH enzymes
    
    Mad/YiiD malonyl-ACP decarboxylase routeMetabolic Pathwaymad_decarboxylase_route
    
    Parts
    
    1. acetyl-ACP primer formation
    
    Malonyl-ACP decarboxylationReactionmad_acetyl_acp_formation
    
    Annotons
    
    Mad/YiiD malonyl-ACP decarboxylase Family: Mad/YiiD-family malonyl-ACP decarboxylases
    
    2. acetyl-ACP condensation
    
    Acetyl-ACP and malonyl-ACP condensationReactionmad_route_first_condensation
    
    Annotons
    
    FabB/FabF-family first condensation Family: FabB/FabF elongation condensing enzymes
9. 5. iterative acyl-chain elongation
10. Four-reaction FAS-II elongation cycleMetabolic Pathwayelongation_cycle
  
  Parts
  1. 1. decarboxylative condensation
  2. KAS-I/KAS-II condensationReactionelongation_condensation
    
    Variants
    
    Elongation condensing-enzyme variants by condensing enzyme (One Or More)
    
    FabB KAS-IReactionfabB_kasI_variant
    
    Annotons
    
    FabB 3-oxoacyl-ACP synthase Family: FabB/KAS-I condensing enzymes
    
    FabF KAS-IIReactionfabF_kasII_variant
    
    Annotons
    
    FabF 3-oxoacyl-ACP synthase Family: FabF/KAS-II condensing enzymes
  3. 2. beta-keto reduction
  4. 3-oxoacyl-ACP reductionReactionbeta_keto_reduction
    
    Variants
    
    3-oxoacyl-ACP reductase variants by enzyme family / compartment (One Or More)
    
    Bacterial FabG reductaseReactionfabG_reductase_variant
    
    Annotons
    
    FabG-family 3-oxoacyl-ACP reductase Family: FabG-family 3-oxoacyl-ACP reductases
    
    Mitochondrial OAR1-type reductaseReactionmito_oar_reductase_variant
    
    Annotons
    
    OAR1-family mitochondrial 3-oxoacyl-ACP reductase Family: fungal mitochondrial 3-oxoacyl-ACP reductases (SDR)
  5. 3. 3-hydroxyacyl dehydration
  6. 3-hydroxyacyl-ACP dehydrationReactionhydroxyacyl_dehydration
    
    Variants
    
    FAS-II dehydratase variants by dehydratase family (One Or More)
    
    FabZ dehydrataseReactionfabZ_dehydratase_variant
    
    Annotons
    
    FabZ 3-hydroxyacyl-ACP dehydratase Family: FabZ-family FAS-II dehydratases
    
    FabA dehydrataseReactionfabA_dehydratase_variant
    
    Annotons
    
    FabA 3-hydroxyacyl-ACP dehydratase Family: FabA-family dehydratase/isomerases
    
    Mitochondrial HTD2 hotdog-fold dehydrataseReactionhtd2_mito_dehydratase_variant
    
    Annotons
    
    HTD2 mitochondrial 3-hydroxyacyl-thioester dehydratase 2 Family: fungal mitochondrial hydroxyacyl-thioester dehydratase type 2
  7. 4. enoyl reduction
  8. Enoyl-ACP reductionReactionenoyl_reduction
    
    Variants
    
    Enoyl-ACP reductase variants by electron donor and enzyme family (One Or More)
    
    FabI NADH-dependent reductaseReactionfabI_nadh_variant
    
    Annotons
    
    FabI enoyl-ACP reductase Family: FabI-family NADH-dependent enoyl-ACP reductases
    
    FabK flavin-dependent reductaseReactionfabK_nadh_variant
    
    Annotons
    
    FabK enoyl-ACP reductase Family: FabK-family flavin-dependent enoyl-ACP reductases
    
    FabV NADH-dependent reductaseReactionfabV_nadh_variant
    
    Annotons
    
    FabV enoyl-ACP reductase Family: NADH-dependent bacterial enoyl-ACP reductases
    
    FabL-like NADPH-dependent reductaseReactionfabL_nadph_variant
    
    Annotons
    
    FabL-like enoyl-ACP reductase Family: FabL-like NADPH-dependent enoyl-ACP reductases
    
    Mitochondrial MECR/ETR1 NADPH-dependent reductaseReactionmecr_etr1_nadph_variant
    
    Annotons
    
    ETR1/MECR mitochondrial 2-enoyl thioester reductase Family: mitochondrial 2-enoyl thioester reductases (MDR superfamily)
11. 6. cis-unsaturated fatty-acid branch optional
12. FabA/FabB cis-unsaturated branchMetabolic Pathwaycis_unsaturated_branch
  
  Parts
  1. 1. trans-2 to cis-3 isomerization
  2. FabA trans-2-decenoyl-ACP isomerizationReactionfabA_double_bond_isomerization
    
    Annotons
    
    FabA trans-2-decenoyl-ACP isomerase Family: FabA-family dehydratase/isomerases
  3. 2. cis-unsaturated chain extension
  4. FabB unsaturated-chain condensationReactionfabB_unsaturated_condensation
    
    Annotons
    
    FabB cis-unsaturated chain elongation Family: FabB/KAS-I condensing enzymes

Details

Type-II fatty-acid synthesisMetabolic Pathwaytype_ii_fatty_acid_synthesis

fatty acid biosynthetic processGO:0006633

ALIGN (YeastPathways project, 2026-10): added eukaryotic mitochondrial FAS II. YeastCyc FASYN-ELONG2-PWY ("fatty acid elongation") is a generic ACP-based elongation round that mixes cytosolic FAS1/FAS2 with the mitochondrial FAS II enzymes CEM1 and OAR1; the FAS1/FAS2 assignments belong to fatty_acid_de_novo_synthesis and are not used here. Mitochondrial representatives (S. cerevisiae, S. pombe from PomBase model 678073a900002931) were added to shared roles where the family matches: ACP (ACP1, SPAC4H3.09 in PTHR20863), malonyl-CoA:ACP transacylase (MCT1, mct1; descriptor has no PANTHER id because human MCAT is in PTHR47170 while yeast MCT1 is in PTHR42681), and the FabF/KAS-II variant (CEM1, cem1 in PTHR11712:SF336, whose "MITOCHONDRIAL" label now also matches these members). New variants were added where the mitochondrial enzyme belongs to a different family: a mitochondrial homomeric acetyl-CoA carboxylase (HFA1, PTHR45728; PMID:14761959), an OAR1-type ketoreductase (PTHR42760:SF133), an HTD2 hotdog dehydratase (PTHR28152) and a MECR/ETR1 NADPH-dependent enoyl reductase (PTHR43981, GO:0141148). Mitochondrial leaves are located in mitochondrion; mitochondrial ACP activation by PPT2 (S. pombe ppt2) is activation context. YeastCyc corrections: HTD2, ETR1, MCT1, ACP1 and HFA1 are missing from FASYN-ELONG2-PWY; HFA1, MCT1, CEM1 and OAR1 are instead listed as catalysts of the cytosolic FAS frames. GO-CAM disagreements: YeastPathways_FASYN-ELONG2-PWY places CEM1 and OAR1 in cytosol, attaches them to the same nodes as cytosolic FAS2, types the FAS1 dehydratase node (3-HYDROXYDECANOYL-ACP-DEHYDR-RXN) as enoyl-ACP reductase GO:0141148 and TES1 as palmitoyl-(protein) hydrolase GO:0008474, and uses GO:0030497 fatty acid elongation as the process. The PomBase model agrees with the mitochondrial FAS II chain but places cut6 (cytosolic ACC) and fas1 acetyltransferase activities in the mitochondrion; S. pombe has no HFA1 paralog in this model. Human mtFAS (OXSM, MCAT, CBR4/HSD17B8, HTD2, MECR, NDUFAB1) is not fully represented: only MECR shares a PANTHER family with its fungal counterpart among the added roles. Exact KT2440 accessions are representative members and do not restrict the module to Pseudomonas. Same-family paralogs without a distinct, supported pathway role remain gene-level curation questions rather than separate module variants. ACP phosphopantetheinylation is required before use but is activation context outside this pathway boundary. FabI is grounded to the functionally appropriate PTHR43159 parent and PAINT node PTN001215190 because the current SF2 name is chloroplast-biased even though the subfamily contains bacterial FabI. PANTHER's assignments for the FabK exemplar (PTHR32332:SF20, a broad 2-nitropropane-dioxygenase-like group) and the FabL exemplar (PTHR43639:SF1, a broad SDR group) are deliberately not used to delimit those variants; experimentally characterized UniProt accessions are retained as exemplars. The compact cis_unsaturated_branch is integration context only; bacterial_unsaturated_fatty_acid_biosynthesis is authoritative for the branch-specific FabA/FabB chemistry and optional FabF extension. PANTHER's broad PTHR11712:SF336 subfamily contains bacterial FabF, KasA/KasB, polyketide-synthase components, and genuine mitochondrial KAS proteins. Its official "MITOCHONDRIAL" label is retained verbatim, while the reviewed bacterial exemplars and exact leaf function constrain the intended FabF role; the label is not a localization assertion for the module. The Mad-route condensing-enzyme descriptor remains at parent PTHR11712 because it intentionally spans FabB and FabF representatives in different subfamilies. The existing fatty_acid_de_novo_synthesis module describes type-I mammalian lipogenesis and is intentionally separate.

Connections

acetyl_coa_carboxylation -> malonyl_acp_loading Provides Input For

AccABCD supplies malonyl-CoA to FabD.

acp_carrier_role -> malonyl_acp_loading Provides Input For

Holo-ACP accepts malonate from FabD.

malonyl_acp_loading -> chain_initiation Provides Input For

Malonyl-ACP is the two-carbon donor for chain initiation.

chain_initiation -> elongation_cycle Provides Input For

The initiated beta-ketoacyl-ACP enters reductive elongation.

elongation_cycle -> cis_unsaturated_branch Provides Input For

A C10 trans-2-enoyl-ACP intermediate can enter the FabA/FabB branch.

Part 1: malonyl-CoA formation

Acetyl-CoA carboxylaseReactionacetyl_coa_carboxylation

Bacteria use a heteromeric AccABCD complex; the mitochondrial FAS II of fungi uses a mitochondrially targeted homomeric multidomain carboxylase (S. cerevisiae HFA1).

Variant set: Acetyl-CoA carboxylase architecture by enzyme architecture / compartment (Exactly One)

Heteromeric bacterial AccABCD carboxylaseProtein Complexheteromeric_accabcd_variant

Annotons

Heteromeric acetyl-CoA carboxylase

accABCD_complex

Participant: Protein Complex: bacterial AccABCD acetyl-CoA carboxylase

Protein Complex:

bacterial AccABCD acetyl-CoA carboxylaseGO:0009317 Heteromeric bacterial complex containing biotin carboxylase AccC, biotin-carrier AccB, and AccA/AccD carboxyltransferase subunits.

Active units:

AccC biotin carboxylase

Participant: Family: bacterial AccC biotin carboxylases

Family:

bacterial AccC biotin carboxylases

Representative Members: PSEPK AccCUniProtKB:Q88QD6

Role: ATP-dependent carboxylation of the AccB-bound biotin cofactor.

Function:

biotin carboxylase activityGO:0004075

AccB biotin-carrier subunit

Participant: Family: bacterial AccB biotin-carrier proteins

Family:

bacterial AccB biotin-carrier proteins

Representative Members: PSEPK AccBUniProtKB:Q88QD5

Role: Covalently carries biotin between the two half-reactions.

AccA carboxyltransferase alpha subunit

Participant: Family: bacterial AccA carboxyltransferase alpha subunits

Family:

bacterial AccA carboxyltransferase alpha subunits

Representative Members: PSEPK AccAUniProtKB:Q88MG4

Role: Alpha component of the acetyl-CoA carboxyltransferase.

AccD carboxyltransferase beta subunit

Participant: Family: bacterial AccD carboxyltransferase beta subunits

Family:

bacterial AccD carboxyltransferase beta subunits

Representative Members: PSEPK AccDUniProtKB:Q88LD9

Role: Beta component of the acetyl-CoA carboxyltransferase.

Function

acetyl-CoA carboxylase activityGO:0003989

Substrates: acetyl-CoA hydrogencarbonate ATP

Products: malonyl-CoA ADP phosphate

Produces the malonyl-CoA two-carbon donor for FAS-II.

Mitochondrial homomeric multidomain carboxylase (fungal HFA1)Reactionmitochondrial_homomeric_acc_variant

Annotons

HFA1: mitochondrial acetyl-CoA carboxylase

hfa1_mito_acc_activity

Participant: Family: eukaryotic multidomain acetyl-CoA carboxylase family (mitochondrial isoform)

Family:

eukaryotic multidomain acetyl-CoA carboxylase family (mitochondrial isoform)PANTHER:PTHR45728

Representative Members: HFA1 (Saccharomyces cerevisiae)UniProtKB:P32874

Function

acetyl-CoA carboxylase activityGO:0003989

Substrates: acetyl-CoA hydrogencarbonate ATP

Products: malonyl-CoA ADP phosphate

Locations

mitochondrionGO:0005739

Supplies the intramitochondrial malonyl-CoA pool for mitochondrial FAS II.

Part 2: acyl-group carriage

Acyl carrier proteinMolecular Functionacp_carrier_role

Annotons

Holo-acyl carrier protein

acpP_carrier

Participant: Family: FAS-II acyl carrier proteins (bacterial AcpP and mitochondrial ACP)

Family:

FAS-II acyl carrier proteins (bacterial AcpP and mitochondrial ACP)PANTHER:PTHR20863

Representative Members: PSEPK AcpPUniProtKB:Q88LL5 ACP1 (Saccharomyces cerevisiae; mitochondrial)UniProtKB:P32463 SPAC4H3.09 (Schizosaccharomyces pombe; mitochondrial)UniProtKB:Q10217

Function

acyl carrier activityGO:0000036

Carries malonyl and growing acyl chains on a phosphopantetheine prosthetic group between dissociated enzymes. The mitochondrial ACP is activated by a mitochondrial phosphopantetheinyl transferase (S. cerevisiae PPT2), which is activation context outside this boundary.

Part 3: malonyl-ACP formation

FabD malonyl-ACP loadingReactionmalonyl_acp_loading

Annotons

Malonyl-CoA:ACP transacylase

fabD_transacylase

Participant: Family: FabD-like malonyl-CoA:ACP transacylases (bacterial and mitochondrial)

Family:

FabD-like malonyl-CoA:ACP transacylases (bacterial and mitochondrial)

Representative Members: PSEPK FabDUniProtKB:Q88LL7 MCT1 (Saccharomyces cerevisiae; mitochondrial)UniProtKB:Q12283 mct1 (Schizosaccharomyces pombe; mitochondrial)UniProtKB:O13698

Function

acyl-carrier-protein S-malonyltransferase activityGO:0004314

Substrates: malonyl-CoA holo-ACP

Products: malonyl-ACP CoA

Loads the two-carbon donor onto ACP.

Part 4: fatty-acid chain initiation

Alternative FAS-II chain-initiation routesMetabolic Pathwaychain_initiation

Bacterial FAS-II systems can form the first beta-ketoacyl-ACP through a FabH-like KAS-III reaction or can first generate an acetyl-ACP primer with a Mad/YiiD-family malonyl-ACP decarboxylase.

Variant set: Fatty-acid chain-initiation route by primer source and initiating enzyme chemistry (One Or More)

KAS-III acyl-CoA-dependent initiationReactionkasIII_route

Variant set: KAS-III acyl-CoA substrate variants by acyl-CoA primer range (One Or More)

FabH1 short-chain-acyl-CoA initiationReactionfabH1_short_chain_variant

Annotons

FabH1 beta-ketoacyl-ACP synthase III

fabH1_initiator

Participant: Family: FabH-like beta-ketoacyl-ACP synthase III enzymes

Family:

FabH-like beta-ketoacyl-ACP synthase III enzymes

Representative Members: PSEPK FabH1UniProtKB:Q88ES4

Function

beta-ketoacyl-acyl-carrier-protein synthase III activityGO:0033818

Substrates: acetyl-CoA malonyl-ACP

Products: acetoacetyl-ACP CoA carbon dioxide

Uses a short-chain acyl-CoA primer to form the first beta-ketoacyl-ACP.

FabH2 medium-chain-acyl-CoA initiationReactionfabH2_medium_chain_variant

Annotons

FabH2 beta-ketodecanoyl-ACP synthase

fabH2_initiator

Participant: Family: medium-chain-acyl-CoA-selective FabH enzymes

Family:

medium-chain-acyl-CoA-selective FabH enzymes

Representative Members: PSEPK FabH2UniProtKB:Q88EC1

Function

beta-ketodecanoyl-acyl-carrier-protein synthase activityGO:0061990

Substrates: octanoyl-CoA malonyl-ACP

Products: 3-oxodecanoyl-ACP CoA carbon dioxide

Uses a medium-chain acyl-CoA primer to enter FAS-II at a correspondingly longer chain length.

Mad/YiiD malonyl-ACP decarboxylase routeMetabolic Pathwaymad_decarboxylase_route

Mad-family decarboxylation creates acetyl-ACP, which a FabB/FabF-like condensing enzyme extends with malonyl-ACP.

Connections

mad_acetyl_acp_formation -> mad_route_first_condensation Provides Input For

Mad-generated acetyl-ACP is the primer for condensation.

Part 1: acetyl-ACP primer formation

Malonyl-ACP decarboxylationReactionmad_acetyl_acp_formation

Annotons

Mad/YiiD malonyl-ACP decarboxylase

mad_malonyl_acp_decarboxylase

Participant: Family: Mad/YiiD-family malonyl-ACP decarboxylases

Family:

Mad/YiiD-family malonyl-ACP decarboxylases

Representative Members: PSEPK MadBUniProtKB:Q88R72

Function

malonyl-ACP decarboxylase activityGO:0016831

Substrates: malonyl-ACP proton

Products: acetyl-ACP carbon dioxide

Produces an ACP-bound acetyl primer without an acyl-CoA.

Part 2: acetyl-ACP condensation

Acetyl-ACP and malonyl-ACP condensationReactionmad_route_first_condensation

Annotons

FabB/FabF-family first condensation

mad_route_kas_condensation

Participant: Family: FabB/FabF elongation condensing enzymes

Family:

FabB/FabF elongation condensing enzymesPANTHER:PTHR11712

Representative Members: PSEPK FabBUniProtKB:Q88FC3 PSEPK FabFUniProtKB:Q88LL4

Function

3-oxoacyl-acyl-carrier-protein synthase activityGO:0004315

Substrates: acetyl-ACP malonyl-ACP

Products: acetoacetyl-ACP holo-ACP carbon dioxide

Converts the Mad-generated primer into the first beta-ketoacyl-ACP.

Part 5: iterative acyl-chain elongation

Four-reaction FAS-II elongation cycleMetabolic Pathwayelongation_cycle

Each round adds two carbons through condensation, beta-keto reduction, dehydration, and enoyl reduction.

Connections

elongation_condensation -> beta_keto_reduction Provides Input For

Condensation produces 3-oxoacyl-ACP for reduction.

beta_keto_reduction -> hydroxyacyl_dehydration Provides Input For

Reduction produces 3-hydroxyacyl-ACP for dehydration.

hydroxyacyl_dehydration -> enoyl_reduction Provides Input For

Dehydration produces trans-2-enoyl-ACP for reduction.

enoyl_reduction -> elongation_condensation Provides Input For

The saturated acyl-ACP product re-enters another elongation round.

Part 1: decarboxylative condensation

KAS-I/KAS-II condensationReactionelongation_condensation

FabB- and FabF-like condensing enzymes are represented as reusable family alternatives. Additional same-function paralogs are adjudicated in gene reviews rather than promoted to separate module variants without a distinct pathway role.

Variant set: Elongation condensing-enzyme variants by condensing enzyme (One Or More)

FabB KAS-IReactionfabB_kasI_variant

Annotons

FabB 3-oxoacyl-ACP synthase

fabB_condensing_activity

Participant: Family: FabB/KAS-I condensing enzymes

Family:

FabB/KAS-I condensing enzymesPANTHER:PTHR11712:SF306

Representative Members: PSEPK FabBUniProtKB:Q88FC3 experimentally characterized E. coli FabBUniProtKB:P0A953

Function

3-oxoacyl-acyl-carrier-protein synthase activityGO:0004315

Substrates: acyl-ACP malonyl-ACP

Products: two-carbon-extended 3-oxoacyl-ACP carbon dioxide

FabF KAS-IIReactionfabF_kasII_variant

Annotons

FabF 3-oxoacyl-ACP synthase

fabF_condensing_activity

Participant: Family: FabF/KAS-II condensing enzymes

Family:

FabF/KAS-II condensing enzymesPANTHER:PTHR11712:SF336

Representative Members: PSEPK FabFUniProtKB:Q88LL4 experimentally characterized E. coli FabFUniProtKB:P0AAI5 CEM1 (Saccharomyces cerevisiae; mitochondrial KAS)UniProtKB:P39525 cem1 (Schizosaccharomyces pombe; mitochondrial KAS)UniProtKB:O94297

Function

3-oxoacyl-acyl-carrier-protein synthase activityGO:0004315

Substrates: acyl-ACP malonyl-ACP

Products: two-carbon-extended 3-oxoacyl-ACP carbon dioxide

Part 2: beta-keto reduction

3-oxoacyl-ACP reductionReactionbeta_keto_reduction

Variant set: 3-oxoacyl-ACP reductase variants by enzyme family / compartment (One Or More)

Bacterial FabG reductaseReactionfabG_reductase_variant

Annotons

FabG-family 3-oxoacyl-ACP reductase

fabG_reductase

Participant: Family: FabG-family 3-oxoacyl-ACP reductases

Family:

FabG-family 3-oxoacyl-ACP reductases

Representative Members: PSEPK FabGUniProtKB:Q88LL6

Function

3-oxoacyl-acyl-carrier-protein reductase (NADPH) activityGO:0004316

Substrates: 3-oxoacyl-ACP NADPH

Products: 3-hydroxyacyl-ACP NADP+

The canonical FabG reaction; family assignment alone is insufficient for promoting other SDR paralogs to this role.

Mitochondrial OAR1-type reductaseReactionmito_oar_reductase_variant

Annotons

OAR1-family mitochondrial 3-oxoacyl-ACP reductase

oar1_mito_reductase

Participant: Family: fungal mitochondrial 3-oxoacyl-ACP reductases (SDR)

Family:

fungal mitochondrial 3-oxoacyl-ACP reductases (SDR)PANTHER:PTHR42760:SF133

Representative Members: OAR1 (Saccharomyces cerevisiae)UniProtKB:P35731 oar2 (Schizosaccharomyces pombe)UniProtKB:O42866

Function

3-oxoacyl-acyl-carrier-protein reductase (NADPH) activityGO:0004316

Substrates: 3-oxoacyl-ACP NADPH

Products: (3R)-3-hydroxyacyl-ACP NADP+

Locations

mitochondrionGO:0005739

Mitochondrial FAS II beta-keto reduction; mammals use a heterotetrameric reductase instead (not represented).

Part 3: 3-hydroxyacyl dehydration

3-hydroxyacyl-ACP dehydrationReactionhydroxyacyl_dehydration

Variant set: FAS-II dehydratase variants by dehydratase family (One Or More)

FabZ dehydrataseReactionfabZ_dehydratase_variant

Annotons

FabZ 3-hydroxyacyl-ACP dehydratase

fabZ_dehydratase

Participant: Family: FabZ-family FAS-II dehydratases

Family:

FabZ-family FAS-II dehydratasesPANTHER:PTHR30272:SF1

Representative Members: PSEPK FabZUniProtKB:Q88MG9 experimentally characterized E. coli FabZUniProtKB:P0A6Q6

Function

(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activityGO:0019171

Substrates: 3-hydroxyacyl-ACP

Products: trans-2-enoyl-ACP H2O

FabA dehydrataseReactionfabA_dehydratase_variant

Annotons

FabA 3-hydroxyacyl-ACP dehydratase

fabA_dehydratase

Participant: Family: FabA-family dehydratase/isomerases

Family:

FabA-family dehydratase/isomerasesPANTHER:PTHR30272:SF8

Representative Members: PSEPK FabAUniProtKB:Q88FC4 experimentally characterized E. coli FabAUniProtKB:P0A6Q3

Function

(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activityGO:0019171

Substrates: 3-hydroxyacyl-ACP

Products: trans-2-enoyl-ACP H2O

Mitochondrial HTD2 hotdog-fold dehydrataseReactionhtd2_mito_dehydratase_variant

Annotons

HTD2 mitochondrial 3-hydroxyacyl-thioester dehydratase 2

htd2_mito_dehydratase

Participant: Family: fungal mitochondrial hydroxyacyl-thioester dehydratase type 2

Family:

fungal mitochondrial hydroxyacyl-thioester dehydratase type 2PANTHER:PTHR28152

Representative Members: HTD2 (Saccharomyces cerevisiae)UniProtKB:P38790 htd2 (Schizosaccharomyces pombe)UniProtKB:Q9Y814

Function

(3R)-hydroxyacyl-acyl-carrier-protein dehydratase activityGO:0019171

Substrates: (3R)-3-hydroxyacyl-ACP

Products: trans-2-enoyl-ACP H2O

Locations

mitochondrionGO:0005739

Mitochondrial FAS II dehydration. The human HTD2 is placed by PANTHER in a different family (PTHR43437), so it is not listed under this family descriptor.

Part 4: enoyl reduction

Enoyl-ACP reductionReactionenoyl_reduction

Variant set: Enoyl-ACP reductase variants by electron donor and enzyme family (One Or More)

FabI NADH-dependent reductaseReactionfabI_nadh_variant

Annotons

FabI enoyl-ACP reductase

fabI_reductase

Participant: Family: FabI-family NADH-dependent enoyl-ACP reductases

Family:

FabI-family NADH-dependent enoyl-ACP reductasesPANTHER:PTHR43159

Representative Members: Escherichia coli FabIUniProtKB:P0AEK4

Function

enoyl-acyl-carrier-protein reductase (NADH) activityGO:0004318

Substrates: trans-2-enoyl-ACP NADH

Products: saturated acyl-ACP NAD+

FabK flavin-dependent reductaseReactionfabK_nadh_variant

Annotons

FabK enoyl-ACP reductase

fabK_reductase

Participant: Family: FabK-family flavin-dependent enoyl-ACP reductases

Family:

FabK-family flavin-dependent enoyl-ACP reductases

Representative Members: Streptococcus pneumoniae R6 FabKUniProtKB:Q8DR17

Function

enoyl-acyl-carrier-protein reductase (NADH) activityGO:0004318

Substrates: trans-2-enoyl-ACP NADH

Products: saturated acyl-ACP NAD+

Cofactors: FMN

FabV NADH-dependent reductaseReactionfabV_nadh_variant

Annotons

FabV enoyl-ACP reductase

fabV_reductase

Participant: Family: NADH-dependent bacterial enoyl-ACP reductases

Family:

NADH-dependent bacterial enoyl-ACP reductasesPANTHER:PTHR37480:SF1

Representative Members: PSEPK FabVUniProtKB:Q88E33

Function

enoyl-acyl-carrier-protein reductase (NADH) activityGO:0004318

Substrates: trans-2-enoyl-ACP NADH

Products: saturated acyl-ACP NAD+

FabL-like NADPH-dependent reductaseReactionfabL_nadph_variant

Annotons

FabL-like enoyl-ACP reductase

fabL_reductase

Participant: Family: FabL-like NADPH-dependent enoyl-ACP reductases

Family:

FabL-like NADPH-dependent enoyl-ACP reductases

Representative Members: Bacillus subtilis FabLUniProtKB:P71079

Function

enoyl-acyl-carrier-protein reductase (NADPH) activityGO:0141148

Substrates: trans-2-enoyl-ACP NADPH

Products: saturated acyl-ACP NADP+

Mitochondrial MECR/ETR1 NADPH-dependent reductaseReactionmecr_etr1_nadph_variant

Annotons

ETR1/MECR mitochondrial 2-enoyl thioester reductase

etr1_mito_reductase

Participant: Family: mitochondrial 2-enoyl thioester reductases (MDR superfamily)

Family:

mitochondrial 2-enoyl thioester reductases (MDR superfamily)PANTHER:PTHR43981

Representative Members: ETR1 (Saccharomyces cerevisiae)UniProtKB:P38071 etr1 (Schizosaccharomyces pombe)UniProtKB:Q10488 MECR (human)UniProtKB:Q9BV79

Function

enoyl-acyl-carrier-protein reductase (NADPH) activityGO:0141148

Substrates: trans-2-enoyl-ACP NADPH

Products: saturated acyl-ACP NADP+

Locations

mitochondrionGO:0005739

Mitochondrial FAS II enoyl reduction by a medium-chain dehydrogenase/reductase unrelated to FabI.

Part 6: cis-unsaturated fatty-acid branch (optional)

FabA/FabB cis-unsaturated branchMetabolic Pathwaycis_unsaturated_branch

Connections

fabA_double_bond_isomerization -> fabB_unsaturated_condensation Provides Input For

FabA supplies cis-3-decenoyl-ACP to FabB.

Part 1: trans-2 to cis-3 isomerization

FabA trans-2-decenoyl-ACP isomerizationReactionfabA_double_bond_isomerization

Annotons

FabA trans-2-decenoyl-ACP isomerase

fabA_isomerase

Participant: Family: FabA-family dehydratase/isomerases

Family:

FabA-family dehydratase/isomerasesPANTHER:PTHR30272:SF8

Representative Members: PSEPK FabAUniProtKB:Q88FC4 experimentally characterized E. coli FabAUniProtKB:P0A6Q3

Function

trans-2-decenoyl-acyl-carrier-protein isomerase activityGO:0034017

Creates cis-3-decenoyl-ACP while bypassing enoyl reduction.

Part 2: cis-unsaturated chain extension

FabB unsaturated-chain condensationReactionfabB_unsaturated_condensation

Annotons

FabB cis-unsaturated chain elongation

fabB_unsaturated_branch

Participant: Family: FabB/KAS-I condensing enzymes

Family:

FabB/KAS-I condensing enzymesPANTHER:PTHR11712:SF306

Representative Members: PSEPK FabBUniProtKB:Q88FC3 experimentally characterized E. coli FabBUniProtKB:P0A953

Function

3-oxoacyl-acyl-carrier-protein synthase activityGO:0004315

Extends cis-3-decenoyl-ACP while preserving cis unsaturation.