polyhydroxybutanoate biosynthesis

MetaCyc:PWY1-3

The core PhaA-PhaB-PhaC route in Cupriavidus necator H16 (called Ralstonia eutropha or Alcaligenes eutrophus H16 in the primary literature) condenses two acetyl-CoA molecules, reduces acetoacetyl-CoA with NADPH to (R)-3-hydroxybutanoyl-CoA, and extends poly[(R)-3-hydroxybutanoate] by one monomer with release of CoA. The graph represents the biosynthetic direction and the core phaCAB enzymes, not every alternative H16 isoenzyme. The polymer node is a chemical class: its input and output edges distinguish chains of length n and n+1 in their descriptions; they are not the same physical chain state.

Pathway type

storage polymer biosynthesis

Organism scope

Cupriavidus necator H16 NCBITaxon:381666

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Pathway network

15 nodes · 20 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Reaction / activity
Chemical / cofactor
Protein / complex
Pathway
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Cupriavidus necator H16 `NCBITaxon:381666`	taxon
acetyl-CoA(4-) `CHEBI:57288`	small molecule
acetoacetyl-CoA(4-) `CHEBI:57286`	small molecule
coenzyme A(4-) `CHEBI:57287`	small molecule
NADPH(4-) `CHEBI:57783`	small molecule
hydron `CHEBI:15378`	small molecule
(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	small molecule
NADP(3-) `CHEBI:58349`	small molecule
poly[(R)-3-hydroxybutanoate] `CHEBI:8298`	polymer
Acetyl-CoA acetyltransferase `UniProtKB:P14611`	protein
Acetoacetyl-CoA reductase `UniProtKB:P14697`	protein
Poly(3-hydroxyalkanoate) polymerase subunit PhaC `UniProtKB:P23608`	protein
acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	molecular activity	left to right
NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	molecular activity	right to left
poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
acetyl-CoA(4-) `CHEBI:57288`	consumes Two acetyl-CoA molecules are condensed; the graph records participation, while the source equation supplies coefficient 2.	acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	RHEA:21037 Source assertion: Rhea assigns CHEBI:57288 to the substrates of the directed reaction RHEA:21037. The source equation has coefficient 2 for acetyl-CoA. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21037']/rh:substrates; rh:contains/rh:compound/rh:chebi`
acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	produces	acetoacetyl-CoA(4-) `CHEBI:57286`	RHEA:21037 Source assertion: Rhea assigns CHEBI:57286 to the products of the directed reaction RHEA:21037. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21037']/rh:products; rh:contains/rh:compound/rh:chebi`
acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	produces	coenzyme A(4-) `CHEBI:57287`	RHEA:21037 Source assertion: Rhea assigns CHEBI:57287 to the products of the directed reaction RHEA:21037. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21037']/rh:products; rh:contains/rh:compound/rh:chebi`
acetoacetyl-CoA(4-) `CHEBI:57286`	consumes	NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	RHEA:45798 Source assertion: Rhea assigns CHEBI:57286 to the substrates of the directed reaction RHEA:45798. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rh:substrates; rh:contains/rh:compound/rh:chebi`
NADPH(4-) `CHEBI:57783`	consumes	NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	RHEA:45798 Source assertion: Rhea assigns CHEBI:57783 to the substrates of the directed reaction RHEA:45798. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rh:substrates; rh:contains/rh:compound/rh:chebi`
hydron `CHEBI:15378`	consumes	NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	RHEA:45798 Source assertion: Rhea assigns CHEBI:15378 to the substrates of the directed reaction RHEA:45798. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rh:substrates; rh:contains/rh:compound/rh:chebi`
NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	produces	(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	RHEA:45798 Source assertion: Rhea assigns CHEBI:57315 to the products of the directed reaction RHEA:45798. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rh:products; rh:contains/rh:compound/rh:chebi`
NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	produces	NADP(3-) `CHEBI:58349`	RHEA:45798 Source assertion: Rhea assigns CHEBI:58349 to the products of the directed reaction RHEA:45798. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rh:products; rh:contains/rh:compound/rh:chebi`
(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	consumes	poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	RHEA:15406 Source assertion: Rhea assigns CHEBI:57315 to the substrates of the directed reaction RHEA:15406. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rh:substrates; rh:contains/rh:compound/rh:chebi`
poly[(R)-3-hydroxybutanoate] `CHEBI:8298`	consumes The input is the poly[(R)-3-hydroxybutanoate] chain of length n. CHEBI:8298 is the shared polymer class, not an identifier for a particular chain length.	poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	RHEA:15406 Source assertion: Rhea assigns CHEBI:8298 to the substrates of the directed reaction RHEA:15406. The substrate polymer is POLYMER:14464, [(3R)-hydroxybutanoate](n), linked to CHEBI:8298. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rh:substrates; rh:contains/rh:compound/rh:underlyingChebi; rh:polymerizationIndex`
poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	produces The output is the extended poly[(R)-3-hydroxybutanoate] chain of length n+1, distinct from the input chain state despite sharing the generic polymer class identifier.	poly[(R)-3-hydroxybutanoate] `CHEBI:8298`	RHEA:15406 Source assertion: Rhea assigns CHEBI:8298 to the products of the directed reaction RHEA:15406. The product polymer is POLYMER:14465, [(3R)-hydroxybutanoate](n+1), linked to CHEBI:8298. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rh:products; rh:contains/rh:compound/rh:underlyingChebi; rh:polymerizationIndex`
poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	produces	coenzyme A(4-) `CHEBI:57287`	RHEA:15406 Source assertion: Rhea assigns CHEBI:57287 to the products of the directed reaction RHEA:15406. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rh:products; rh:contains/rh:compound/rh:chebi`
Acetyl-CoA acetyltransferase `UniProtKB:P14611`	catalyzes	acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	UniProtKB:P14611 Source assertion: UniProt assigns PhaA to RHEA:21036 (ECO:0000269 and ECO:0000255) and describes condensation of two acetyl-CoA units. RHEA:21037 is the selected biosynthetic direction. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction[reactionCrossReferences.id='RHEA:21036']; comments[commentType='FUNCTION']` PMID:2670935 beta-ketothiolase and acetoacetyl-CoA reductase enzyme activities Source location `Abstract`
Acetoacetyl-CoA reductase `UniProtKB:P14697`	catalyzes	NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	UniProtKB:P14697 Source assertion: UniProt assigns PhaB to the specific RHEA:45796 acetoacetyl-CoA reaction; its FUNCTION statement supports chiral reduction to (R)-3-hydroxybutyryl-CoA with ECO:0000269. RHEA:45798 is the biosynthetic direction. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction[reactionCrossReferences.id='RHEA:45796']; comments[commentType='FUNCTION']` PMID:23913421 PhaB forms a ternary complex with NADPH and acetoacetyl-CoA. Source location `Abstract`
Poly(3-hydroxyalkanoate) polymerase subunit PhaC `UniProtKB:P23608`	catalyzes	poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	UniProtKB:P23608 Source assertion: UniProt assigns PhaC to RHEA:15405 with ECO:0000250; its FUNCTION statement independently describes PHB polymerization with ECO:0000269. The directed chain-extension reaction is RHEA:15406. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction[reactionCrossReferences.id='RHEA:15405']; comments[commentType='FUNCTION']` PMID:22369488 catalyzes the formation of PHB from (R)-3-hydroxybutyryl-CoA Source location `Abstract`
acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	part_of	`MetaCyc:PWY1-3`	MetaCyc:PWY1-3 Source assertion: MetaCyc PWY1-3 declares native reaction ACETYL-COA-ACETYLTRANSFER-RXN as a pathway member. Source location `Pathway[@frameid='PWY1-3']/reaction-list/Reaction[@frameid='ACETYL-COA-ACETYLTRANSFER-RXN']` RHEA:21037 Source assertion: Rhea links RHEA:21039 to MetaCyc:ACETYL-COA-ACETYLTRANSFER-RXN. Master RHEA:21036 identifies RHEA:21039 as its bidirectional member and RHEA:21037 as a directional member; RHEA:21037 selects acetyl-CoA condensation. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21039']/rdfs:seeAlso; rdf:Description[@rdf:about='http://rdf.rhea-db.org/21036']/rh:bidirectionalReaction and rh:directionalReaction`
NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	part_of	`MetaCyc:PWY1-3`	MetaCyc:PWY1-3 Source assertion: MetaCyc PWY1-3 declares native reaction RXN-5901 as a pathway member. Source location `Pathway[@frameid='PWY1-3']/reaction-list/Reaction[@frameid='RXN-5901']` RHEA:45798 Source assertion: Rhea directly cross-references RHEA:45798 to MetaCyc:RXN-5901 in rdfs:seeAlso. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rdfs:seeAlso[@rdf:resource='http://identifiers.org/biocyc/METACYC:RXN-5901']`
poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	part_of	`MetaCyc:PWY1-3`	MetaCyc:PWY1-3 Source assertion: MetaCyc PWY1-3 declares native reaction RXN1-42 as a pathway member. Source location `Pathway[@frameid='PWY1-3']/reaction-list/Reaction[@frameid='RXN1-42']` RHEA:15406 Source assertion: Rhea directly cross-references RHEA:15406 to MetaCyc:RXN1-42 in rdfs:seeAlso. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rdfs:seeAlso[@rdf:resource='http://identifiers.org/biocyc/METACYC:RXN1-42']`
acetyl-CoA condensation to acetoacetyl-CoA `RHEA:21037`	precedes	NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	MetaCyc:PWY1-3 Source assertion: MetaCyc PWY1-3 declares ACETYL-COA-ACETYLTRANSFER-RXN as a predecessor of RXN-5901. Source location `Pathway/reaction-ordering[Reaction/@frameid='RXN-5901']/predecessor-reactions/Reaction[@frameid='ACETYL-COA-ACETYLTRANSFER-RXN']` RHEA:21037 Source assertion: Rhea links RHEA:21039 to MetaCyc:ACETYL-COA-ACETYLTRANSFER-RXN. Master RHEA:21036 identifies RHEA:21039 as its bidirectional member and RHEA:21037 as a directional member; RHEA:21037 selects acetyl-CoA condensation. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21039']/rdfs:seeAlso; rdf:Description[@rdf:about='http://rdf.rhea-db.org/21036']/rh:bidirectionalReaction and rh:directionalReaction` RHEA:45798 Source assertion: Rhea directly cross-references RHEA:45798 to MetaCyc:RXN-5901 in rdfs:seeAlso. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rdfs:seeAlso[@rdf:resource='http://identifiers.org/biocyc/METACYC:RXN-5901']`
NADPH-dependent reduction to (R)-3-hydroxybutanoyl-CoA `RHEA:45798`	precedes	poly[(R)-3-hydroxybutanoate] chain extension from n to n+1 `RHEA:15406`	MetaCyc:PWY1-3 Source assertion: MetaCyc PWY1-3 declares RXN-5901 as a predecessor of RXN1-42. Source location `Pathway/reaction-ordering[Reaction/@frameid='RXN1-42']/predecessor-reactions/Reaction[@frameid='RXN-5901']` RHEA:45798 Source assertion: Rhea directly cross-references RHEA:45798 to MetaCyc:RXN-5901 in rdfs:seeAlso. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/45798']/rdfs:seeAlso[@rdf:resource='http://identifiers.org/biocyc/METACYC:RXN-5901']` RHEA:15406 Source assertion: Rhea directly cross-references RHEA:15406 to MetaCyc:RXN1-42 in rdfs:seeAlso. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15406']/rdfs:seeAlso[@rdf:resource='http://identifiers.org/biocyc/METACYC:RXN1-42']`

References

MetaCyc:PWY1-3 MetaCyc polyhydroxybutanoate biosynthesis (source version: 22.5)
RHEA:21037 Rhea 21037 directed PHB biosynthetic reaction (source version: 142 (2026-09-02))
RHEA:45798 Rhea 45798 directed PHB biosynthetic reaction (source version: 142 (2026-09-02))
RHEA:15406 Rhea 15406 directed PHB biosynthetic reaction (source version: 142 (2026-09-02))
UniProtKB:P14611 UniProtKB P14611, Cupriavidus necator H16 (source version: 2026_03)
UniProtKB:P14697 UniProtKB P14697, Cupriavidus necator H16 (source version: 2026_03)
UniProtKB:P23608 UniProtKB P23608, Cupriavidus necator H16 (source version: 2026_03)
PMID:2670935 Poly-beta-hydroxybutyrate biosynthesis in Alcaligenes eutrophus H16. Characterization of the genes encoding beta-ketothiolase and acetoacetyl-CoA reductase.
PMID:23913421 Directed evolution and structural analysis of NADPH-dependent Acetoacetyl Coenzyme A (Acetoacetyl-CoA) reductase from Ralstonia eutropha reveals two mutations responsible for enhanced kinetics.
PMID:22369488 Purification of polyhydroxybutyrate synthase from its native organism, Ralstonia eutropha: implications for the initiation and elongation of polymer formation in vivo.

Curation history

2026-10-10T20:47:39Z claude-code
- CREATE — Add the evidence-backed core PHB biosynthetic route of Cupriavidus necator H16
  Created MetaCyc PWY1-3 with three directed reactions, eleven participants and twenty evidence-backed edges. Inspected MetaCyc XML, UniProt, Rhea 142 and primary enzyme studies. Preserved chemical stereochemistry, n versus n+1 polymer states in class-level edge evidence, and excluded unreviewed isoenzyme/regulatory claims. Corrected membership and reaction-crosswalk attribution during adversarial review. Shared authority snapshots, generated pages, full gates and independent structured review accompany this addition.
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