3-hydroxypropionate bicycle

traitmech:000023 · CLASS · REVIEWED

An autotrophic carbon-fixation pathway in which two molecules of bicarbonate are fixed via 3-hydroxypropionate and converted to glyoxylate and pyruvate. It is characteristic of the filamentous anoxygenic phototroph Chloroflexus aurantiacus.

Trait evidence (2)

DOI:10.1128/AEM.02473-10
Berg review describes the 3-hydroxypropionate bicycle and its association with Chloroflexus.
DOI:10.1146/annurev-marine-120709-142712
Hügler & Sievert include the 3-hydroxypropionate pathway among autotrophic carbon-fixation strategies.

3-hydroxypropionate bicycle fixes bicarbonate in Chloroflexus

Evidence-backed causal sketch linking bicarbonate fixation via 3-hydroxypropionate to glyoxylate and pyruvate in Chloroflexus aurantiacus.

MECHANISTIC · The graph represents the experimentally completed C. aurantiacus 3HP bicycle. The reviewed mcl/MMC-lyase example supports the terminal trifunctional cleavage node; the other diagnostic multifunctional enzymes remain separately scoped.

Edge evidence

hydrogencarbonate fixed by 3-hydroxypropionate bicycle METPO:2007404
Two molecules of bicarbonate are fixed per cycle turn.
- DOI:10.1128/AEM.02473-10 Berg describes the 3-hydroxypropionate bicycle in Chloroflexus.
3-hydroxypropionate bicycle contributes to carbon fixation RO:0002326
The bicycle is one of the recognized autotrophic CO2-fixation pathways.
- DOI:10.1146/annurev-marine-120709-142712 Hügler & Sievert include the 3-hydroxypropionate pathway among autotrophic carbon-fixation strategies.
acetyl-CoA carboxylase causally upstream of malonyl-CoA
Acetyl-CoA carboxylase converts acetyl-CoA and bicarbonate to malonyl-CoA at the expense of ATP.
- DOI:10.17192/z2022.0467 acetyl-CoA carboxylase (EC 6.4.1.2) converts acetyl-CoA and bicarbonate to malonyl-CoA.
propionyl-CoA carboxylase causally upstream of (2S)-methylmalonyl-CoA
Propionyl-CoA carboxylase converts propionyl-CoA and bicarbonate to (2S)-methylmalonyl-CoA at the expense of ATP.
- DOI:10.17192/z2022.0467 propionyl-CoA carboxylase (EC 6.4.1.3) converts propionyl-CoA and bicarbonate to (2S)-methylmalonyl-CoA.
malonyl-CoA reductase causally upstream of 3-hydroxypropionate
Malonyl-CoA reductase reduces malonyl-CoA to 3-hydroxypropionate; central diagnostic enzyme.
- DOI:10.1146/annurev-marine-120709-142712 malonyl-CoA reductase reducing malonyl-CoA to 3-hydroxypropionate.
propionyl-CoA synthase causally upstream of propionyl-CoA
Propionyl-CoA synthase converts 3-hydroxypropionate to propionyl-CoA.
- DOI:10.1146/annurev-marine-120709-142712 propionyl-CoA synthase converting 3-hydroxypropionate to propionyl-CoA.
malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (MMC lyase) causally upstream of pyruvate
MMC lyase cleaves citramalyl-CoA to pyruvate and acetyl-CoA.
- DOI:10.1146/annurev-marine-120709-142712 cleavage of citramalyl-CoA to pyruvate and acetyl-CoA.
malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (MMC lyase) causally upstream of acetyl-CoA
MMC lyase cleavage also yields acetyl-CoA alongside pyruvate.
- DOI:10.1146/annurev-marine-120709-142712 cleavage of citramalyl-CoA to pyruvate and acetyl-CoA.
3-hydroxypropionate bicycle has output pyruvate
Overall the bicycle produces one pyruvate from three bicarbonates.
- DOI:10.1146/annurev-marine-120709-142712 producing one pyruvate from three bicarbonates.
acetyl-CoA carboxylase contributes to 3-hydroxypropionate bicycle RO:0002326
Acetyl-CoA carboxylase is an enzyme of the 3HP bicycle.
- DOI:10.1128/AEM.02473-10 The 3-hydroxypropionate (Fuchs-Holo) bi-cycle. Enzymes: 1, acetyl-CoA carboxylase Verified against the public PMC figure caption.
malonyl-CoA reductase contributes to 3-hydroxypropionate bicycle RO:0002326
Malonyl-CoA reductase is an enzyme of the 3HP bicycle.
- DOI:10.1128/AEM.02473-10 Enzymes: 1, acetyl-CoA carboxylase; 2, malonyl-CoA reductase Verified against the public PMC figure caption.
propionyl-CoA synthase contributes to 3-hydroxypropionate bicycle RO:0002326
Propionyl-CoA synthase is an enzyme of the 3HP bicycle.
- DOI:10.1128/AEM.02473-10 Enzymes: 1, acetyl-CoA carboxylase; 2, malonyl-CoA reductase; 3, propionyl-CoA synthase Verified against the public PMC figure caption.
propionyl-CoA carboxylase contributes to 3-hydroxypropionate bicycle RO:0002326
Propionyl-CoA carboxylase is an enzyme of the 3HP bicycle.
- DOI:10.1128/AEM.02473-10 malonyl-CoA reductase; 3, propionyl-CoA synthase; 4, propionyl-CoA carboxylase Verified against the public PMC figure caption.

Protein and taxon examples

Graph node Protein Taxon UniProt status Role and evidence

malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (MMC lyase)

Graph node	Protein	Taxon	UniProt status	Role and evidence
malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (MMC lyase)	`UniProtKB:S5N020` Malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (mcl)	Chloroflexus aurantiacus `NCBITaxon:1108`	`REVIEWED` retrieved 2026-08-24 · entry v45 · sequence v1	Trifunctional MMC lyase catalyzing malyl-CoA cleavage, beta-methylmalyl-CoA formation, and citramalyl-CoA cleavage in the C. aurantiacus bicycle. `DOI:10.1073/pnas.0908356106` (S)-Citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by a tri-functional lyase The primary pathway-completion study identifies mcl as the trifunctional MMC lyase. UniProtKB S5N020 is the reviewed mcl entry from C. aurantiacus.

UniProtKB:S5N020
Malyl-CoA/beta-methylmalyl-CoA/citramalyl-CoA lyase (mcl)

Chloroflexus aurantiacus
NCBITaxon:1108

REVIEWED
retrieved 2026-08-24 · entry v45 · sequence v1

Trifunctional MMC lyase catalyzing malyl-CoA cleavage, beta-methylmalyl-CoA formation, and citramalyl-CoA cleavage in the C. aurantiacus bicycle.

DOI:10.1073/pnas.0908356106 (S)-Citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by a tri-functional lyase The primary pathway-completion study identifies mcl as the trifunctional MMC lyase. UniProtKB S5N020 is the reviewed mcl entry from C. aurantiacus.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1128/AEM.02473-10

Parent traits (1)

carbon fixation traitmech:000019

Synonyms (1)

3-hydroxypropionate cycle RELATED_SYNONYM · DOI:10.1128/AEM.02473-10

kg-microbe context

Matched 1 kg-microbe node via parent_proxy.

METPO:1000060 [-1.052, -1.766, -1.194, +0.291, …]

512-dim DeepWalkSkipGramEnsmallen embedding from kg-microbe (2026-04-25).

Nearest neighbors in embedding space

Top-8 cosine-similar METPO traits from the 2026-04-25 deepwalk (512-D).

metabolism lignin degradation 1.000
metabolism sulfur oxidation 1.000
metabolism starch degradation 1.000
metabolism reductive tricarboxylic acid cycle 1.000
metabolism proteorhodopsin phototrophy 1.000
metabolism proteolysis 1.000
metabolism phototrophy 1.000
metabolism photosynthesis 1.000

Deep research

Generated by just research-trait; source: research/traits/metabolism/three_hydroxypropionate_bicycle-deep-research-falcon.md

Unreviewed literature output — not curated TraitMech content Ontology identifiers suggested below have not been resolved against their ontologies, and some are known to be wrong. Check any CURIE against the source before using it.

# TraitMech curation report: 3-hydroxypropionate bicycle

## Record and scope

- **Trait:** 3-hydroxypropionate bicycle
- **Identifier:** `traitmech:000023`
- **Category / kind / status:** METABOLISM / CLASS / REVIEWED
- **Synonym:** 3-hydroxypropionate cycle
- **Parent:** `traitmech:000019`

This trait should represent the **complete bacterial Fuchs–Holo 3-hydroxypropionate bicycle**: an autotrophic, cytosolic carbon-assimilation capacity in which two linked cycles fix inorganic carbon through CoA-bound intermediates and generate pyruvate for central metabolism. The first cycle regenerates acetyl-CoA while producing glyoxylate; the second assimilates glyoxylate and again regenerates acetyl-CoA. Overall, three bicarbonate molecules yield one pyruvate, with reported consumption of five ATP and six NADPH at the pathway level. Thirteen enzymes catalyze 19 reactions because several enzymes are multifunctional. (berg2011ecologicalaspectsof pages 7-8, min2022crystalstructureof pages 1-2, hugler2011beyondthecalvin pages 9-10)

The canonical experimentally characterized organism is the filamentous anoxygenic phototroph *Chloroflexus aurantiacus*. It preferentially grows photoheterotrophically but can grow autotrophically in laboratory cultures and hot-spring microbial mats. The bicycle also permits co-assimilation of fermentation products such as acetate, propionate, and succinate and contains no intrinsically oxygen-sensitive step, although a B12-dependent methylmalonyl-CoA mutase may be vulnerable under combined high oxygen and light. (berg2011ecologicalaspectsof pages 8-9, berg2011ecologicalaspectsof pages 7-8)

### Boundary cases

1. **Exclude the archaeal 3-hydroxypropionate/4-hydroxybutyrate cycle.** Its acetyl-CoA-to-succinyl-CoA segment is formally related, but its regeneration arm converts succinyl-CoA through 4-hydroxybutyrate and acetoacetyl-CoA to two acetyl-CoA molecules. It lacks the glyoxylate-assimilation half of the bacterial bicycle and evolved with substantially different enzymes. (berg2011ecologicalaspectsof pages 7-8, hugler2011beyondthecalvin pages 9-10)
2. **Exclude isolated 3HP enzymes or partial modules.** Malonyl-CoA reductase, propionyl-CoA synthase, or related reactions can support assimilation or production of organic compounds without conferring autotrophy. In 27 Actinobacteriota MAGs, average pathway completeness was only 68.6%, and the authors favored organic-substrate assimilation rather than a functional bicycle. (garritano2022carbonfixationpathways pages 2-3)
3. **Do not equate genomic prediction with demonstrated physiology.** Comparative genomics identified candidate complete pathways beyond Chloroflexota—including Ga0077523, Burkholderiaceae, and Gemmatimonadota MAGs—but these remain predictions unless growth, isotope incorporation, flux, or enzyme evidence is available. (garritano2022carbonfixationpathways pages 2-3)
4. **Exclude synthetic HOPAC and Lcm routes.** They borrow 3HP chemistry but are new-to-nature pathways with different topology and products. (schulzmirbach2024newtonatureco2dependentacetylcoa pages 1-2, mclean2023exploringalternativepathways pages 1-2)

## Candidate nodes grouped by type

### Trait and pathway modules

- `traitmech:000023` — 3-hydroxypropionate bicycle
- Glyoxylate-synthesis cycle — label-only module
- Glyoxylate-assimilation cycle — label-only module
- Autotrophic bicarbonate fixation — candidate biological process
- Photoautotrophic growth — candidate phenotype
- Mixotrophic/photoheterotrophic co-assimilation — candidate associated phenotype, not constitutive evidence of the complete bicycle

### Organisms and environments

- *Chloroflexus aurantiacus* — canonical reference taxon; ground to its verified NCBITaxon record during implementation
- *Roseiflexus castenholzii* — source of directly characterized mesaconyl-CoA C1–C4 transferase; taxon-specific supporting evidence
- Chloroflexaceae / Chloroflexota — historically associated clade
- Filamentous anoxygenic phototroph — organismal phenotype/class
- Hot-spring microbial mat — candidate ENVO-grounded environment
- Light — experimental/environmental energy input
- Anoxic or low-oxygen phototrophic conditions — context node
- Oxygen — pathway broadly tolerant, but potentially detrimental to the radical B12 step under intense light

### Chemicals and cofactors

Conservatively ground common metabolites to verified ChEBI records during YAML implementation: bicarbonate, carbon dioxide, acetyl-CoA, malonyl-CoA, 3-hydroxypropionate, propionyl-CoA, methylmalonyl-CoA, succinyl-CoA, glyoxylate, pyruvate, ATP, ADP, NADPH, NADP+, biotin, and cobalamin. Specialized stereochemical intermediates should remain label-only until registry records are checked:

- (S)-malyl-CoA
- (2R,3S)-β-methylmalyl-CoA
- mesaconyl-C1-CoA
- mesaconyl-C4-CoA
- (S)-citramalyl-CoA
- 3-hydroxypropionyl-CoA
- acrylyl-CoA

### Enzymes, proteins, and complexes

- Biotin-dependent acetyl-CoA/propionyl-CoA carboxylase
- Malonyl-CoA reductase (MCR), bifunctional
- Propionyl-CoA synthase (PCS), trifunctional

Showing the first 60 of 214 lines of findings; the linked file also carries the run's front matter and the prompt it was given — read the full report.

Canonical examples (1)

Organisms cited as exemplars of this trait. Taxon ids are NCBITaxon and link out to the NCBI record.

Chloroflexus aurantiacus NCBITaxon:1108 DOI:10.1073/pnas.0908356106 Where the 3-hydroxypropionate bicycle of autotrophic CO2 fixation was discovered (filamentous anoxygenic phototroph).

Curation history

2026-05-30T00:00:00Z · PROPOSED_FROM_RESEARCH · claude
Proposed candidate METABOLISM trait (3-hydroxypropionate bicycle); sub-variant of carbon fixation.
2026-06-10T14:00:00Z · CURATED_CAUSAL_GRAPH · claude
Added evidence-backed causal graph (3HP bicycle bicarbonate fixation) with CHEBI/GO node groundings and RO/METPO predicate groundings; promoted PROPOSED to REVIEWED.
2026-06-23T00:00:00Z · ENRICH_CAUSAL_GRAPH · claude
Added 7 evidence-backed generic edges (11 new nodes) from the deep-research report.
2026-06-24T17:23:33Z · GROUND_CAUSAL_NODES · claude
Grounded 3 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16510×1, CHEBI:15539×1, CHEBI:15361×1).
2026-06-26T07:15:19Z · GROUND_CAUSAL_NODES · claude
Grounded 3 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A059L760×1, UniProtKB:A0A024E6S7×1, UniProtKB:Q6QQP7×1).
2026-07-20T04:21:11Z · RETRACT_DEAD_UNIPROT_GROUNDINGS · claude
Retracted 2 UniProtKB grounding(s) whose accessions are deleted from UniProt; nodes demoted to label-only pending re-grounding (docs/GROUNDING_POLICY.md)
2026-07-20T04:23:54Z · GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0003989×1, GO:0004658×1).
2026-08-22T04:26:15Z · REVIEW_UNIPROT_INSTANCE_GROUNDINGS · codex
Reviewed 1 organism-specific UniProtKB grounding(s): replaced 0 with taxon-agnostic GO/InterPro terms and retracted 1 to label-only where no exact semantic term was supported (docs/GROUNDING_POLICY.md).
2026-08-24T09:45:00Z · CURATE_PROTEIN_TAXON_EXAMPLE · codex
Scoped the C. aurantiacus 3HP bicycle, added a DOI-backed reviewed mcl/MMC-lyase example, and documented the multifunctional MCR, PCS, and MMC-lyase nodes as reviewed label-only where no single exact semantic term represents each fusion.
2026-08-31T09:00:00Z · CONNECT_CAUSAL_GRAPH_COMPONENTS · codex
Resolved issue #183 graph fragmentation (5 components to 1) using 4 public-source, verbatim-snippet-backed connector(s). No paid research service was called.