Bacterial methionine cycle and homocysteine remethylation

A reusable bacterial cycle that converts L-methionine to S-adenosyl-L-methionine (SAM), channels SAM through methyl-transfer reactions that produce S-adenosyl-L-homocysteine (SAH), hydrolyzes SAH to L-homocysteine, and remethylates L-homocysteine to regenerate L-methionine. The boundary begins with methionine adenosylation and ends with methionine regeneration; de novo production of methionine and sulfur assimilation are adjacent pathways rather than parts of this cycle.

MODULE:bacterial_methionine_cycleDRAFTMetabolic Pathwaymodules/bacterial_methionine_cycle.yaml

L-methionine cycleGO:0033353

GO:0033353

L-methionine cycle

GO:0033353 provides the biological-process boundary for cyclic conversion of methionine through SAM, SAH, and homocysteine back to methionine.

KEGG:map00270

Cysteine and methionine metabolism

KEGG map00270 places methionine adenosyltransferase, SAH processing, and homocysteine remethylation within cysteine and methionine metabolism.

UniProtKB:P0AF12

Escherichia coli K-12 MtnN/Pfs UniProt record

The reviewed MtnN/Pfs record assigns the SAH nucleosidase reaction and PANTHER:PTHR46832, corroborating the family selector for the first step of the alternative bacterial SAH-processing route.

UniProtKB:P45578

Escherichia coli K-12 LuxS UniProt record

The reviewed LuxS record assigns S-ribosylhomocysteine lyase activity and PANTHER:PTHR35799, corroborating the family selector for the second step of the alternative bacterial SAH-processing route.

11Nodes

6Parts

2Variant Sets

4Variants

7Annotons

5Connections

Derived QC

Recommended-field compliance

60.0% recommended fields populated

module.knowledge_gaps[0] · status (0/1)
module.knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

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

Leaf nodes lacking representative members

1 leaf node(s) with no concrete protein grounding:

SAM-dependent methyl transfer producing SAH ANY_WITH_FUNCTION

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (4/6 grounded genes reviewed)

4 complete review(s) · 2 with deep research · 2 missing review · 2 reviewed but lacking deep research

Gene	Review	Complete	Deep research
ahcY A0A140FWS3	✓	✓	✗
metE Q88JF1	✓	✓	✓
metH Q88KB5	✓	✓	✓
metK Q88D60	✓	✓	✗
Escherichia coli K-12 MtnN/Pfs P0AF12	✗	—	—
Escherichia coli K-12 LuxS P45578	✗	—	—

Tree

Bacterial methionine cycle and remethylationMetabolic Pathwaybacterial_methionine_cycle

Parts
1. 1. S-adenosyl-L-methionine synthesis
2. Methionine adenosylation to SAMReactionsam_synthesis
  
  Annotons
  - Methionine adenosyltransferase Family: S-adenosylmethionine synthetase family
3. 2. SAM-dependent transmethylation
4. SAM-dependent methyl transfer producing SAHReactiontransmethylation
  
  Annotons
  - SAM-dependent methyltransferase role Any With Function: S-adenosylmethionine-dependent methyltransferase activity
5. 3. S-adenosyl-L-homocysteine processing to homocysteine
6. Alternative bacterial SAH-processing routesMetabolic Pathwaysah_processing
  
  Variants
  1. SAH-processing chemistry by one-step hydrolysis or two-step nucleosidase/lyase route (One Or More)
    
    Direct AhcY hydrolysisReactionahcy_route
    
    Annotons
    
    Adenosylhomocysteinase Family: Adenosylhomocysteinase family
    
    MtnN/Pfs plus LuxS routeMetabolic Pathwaymtnn_luxs_route
    
    Parts
    
    1. SAH nucleoside cleavage
    
    SAH nucleosidase reactionReactionmtnn_step
    
    Annotons
    
    Adenosylhomocysteine nucleosidase Family: MtnN/Pfs nucleosidase family
    
    2. homocysteine release
    
    S-ribosylhomocysteine cleavageReactionluxs_step
    
    Annotons
    
    S-ribosylhomocysteine lyase Family: LuxS family
7. 4. homocysteine remethylation to methionine
8. Folate-dependent methionine regenerationReactionhomocysteine_remethylation
  
  Variants
  1. Methionine synthase route by cobalamin dependence (One Or More)
    
    Cobalamin-dependent MetH routeReactionmeth_variant
    
    Annotons
    
    Cobalamin-dependent methionine synthase Family: Methionine synthase family
    
    Cobalamin-independent MetE routeReactionmete_variant
    
    Annotons
    
    Cobalamin-independent methionine synthase Family: Cobalamin-independent methionine synthase family

Details

Bacterial methionine cycle and remethylationMetabolic Pathwaybacterial_methionine_cycle

L-methionine cycleGO:0033353

This bacterial module is intentionally separate from the existing eukaryotic methionine_cycle, sam_cycle, and homocysteine_metabolism modules. De novo methionine biosynthesis remains in methionine_biosynthesis. Cysteine biosynthesis, transsulfuration, sulfur assimilation, methionine degradation, and methylthioadenosine salvage are outside this cycle boundary.

Connections

sam_synthesis -> transmethylation Provides Input For

SAM produced by MetK is the methyl donor used in transmethylation.

transmethylation -> sah_processing Provides Input For

Transmethylation produces SAH for either bacterial processing route.

sah_processing -> homocysteine_remethylation Provides Input For

Complete SAH processing supplies homocysteine for remethylation.

homocysteine_remethylation -> sam_synthesis Provides Input For

Remethylation regenerates methionine for another cycle.

Part 1: S-adenosyl-L-methionine synthesis

Methionine adenosylation to SAMReactionsam_synthesis

Annotons

Methionine adenosyltransferase

metk_activity

Participant: Family: S-adenosylmethionine synthetase family

Family:

S-adenosylmethionine synthetase familyPANTHER:PTHR11964

Representative Members: PSEPK MetKUniProtKB:Q88D60

Function

methionine adenosyltransferase activityGO:0004478

Substrates: L-methionineCHEBI:57844 ATPCHEBI:30616 waterCHEBI:15377

Products: S-adenosyl-L-methionineCHEBI:59789 phosphateCHEBI:43474 diphosphateCHEBI:33019

Produces the SAM methyl donor from methionine and ATP.

Part 2: SAM-dependent transmethylation

SAM-dependent methyl transfer producing SAHReactiontransmethylation

Annotons

SAM-dependent methyltransferase role

sam_methyltransferase_activity

Participant: Any With Function: S-adenosylmethionine-dependent methyltransferase activity

Required Function:

S-adenosylmethionine-dependent methyltransferase activityGO:0008757 A bacterial methyltransferase that uses SAM as methyl donor and produces SAH; the acceptor varies with the methylation reaction and is not fixed by this cycle module.

Function

SAM-dependent methyltransferase activityGO:0008757

Substrates: S-adenosyl-L-methionineCHEBI:59789 methyl-group acceptor

Products: S-adenosyl-L-homocysteineCHEBI:57856 methylated acceptor

Represents the distributed set of SAM-consuming methylation reactions that generate SAH rather than a single dedicated enzyme.

Part 3: S-adenosyl-L-homocysteine processing to homocysteine

Alternative bacterial SAH-processing routesMetabolic Pathwaysah_processing

Variant set: SAH-processing chemistry by one-step hydrolysis or two-step nucleosidase/lyase route (One Or More)

Direct AhcY hydrolysisReactionahcy_route

Annotons

Adenosylhomocysteinase

ahcy_activity

Participant: Family: Adenosylhomocysteinase family

Family:

Adenosylhomocysteinase familyPANTHER:PTHR23420

Representative Members: PSEPK AhcYUniProtKB:A0A140FWS3

Function

adenosylhomocysteinase activityGO:0004013

Substrates: S-adenosyl-L-homocysteineCHEBI:57856 waterCHEBI:15377

Products: L-homocysteineCHEBI:58199 adenosineCHEBI:16335

Directly hydrolyzes SAH and supplies homocysteine for remethylation.

MtnN/Pfs plus LuxS routeMetabolic Pathwaymtnn_luxs_route

A two-step bacterial route in which MtnN/Pfs converts SAH to S-ribosylhomocysteine and LuxS releases homocysteine. Both steps are required; the nucleosidase alone does not complete SAH conversion to homocysteine.

Connections

mtnn_step -> luxs_step Provides Input For

MtnN/Pfs supplies S-ribosylhomocysteine to LuxS.

Part 1: SAH nucleoside cleavage

SAH nucleosidase reactionReactionmtnn_step

Annotons

Adenosylhomocysteine nucleosidase

mtnn_activity

Participant: Family: MtnN/Pfs nucleosidase family

Family:

MtnN/Pfs nucleosidase familyPANTHER:PTHR46832

Representative Members: Escherichia coli K-12 MtnN/PfsUniProtKB:P0AF12

Function

adenosylhomocysteine nucleosidase activityGO:0008782

Substrates: S-adenosyl-L-homocysteineCHEBI:57856 waterCHEBI:15377

Products: S-ribosyl-L-homocysteineCHEBI:58195 adenineCHEBI:16708

Produces S-ribosylhomocysteine for the required LuxS step; this enzyme can also participate in MTA salvage.

Part 2: homocysteine release

S-ribosylhomocysteine cleavageReactionluxs_step

Annotons

S-ribosylhomocysteine lyase

luxs_activity

Participant: Family: LuxS family

Family:

LuxS familyPANTHER:PTHR35799

Representative Members: Escherichia coli K-12 LuxSUniProtKB:P45578

Function

S-ribosylhomocysteine lyase activityGO:0043768

Substrates: S-ribosyl-L-homocysteineCHEBI:58195

Products: L-homocysteineCHEBI:58199 4,5-dihydroxypentane-2,3-dioneCHEBI:29484

Releases homocysteine from S-ribosylhomocysteine; the second product can cyclize into AI-2 signals.

Part 4: homocysteine remethylation to methionine

Folate-dependent methionine regenerationReactionhomocysteine_remethylation

Variant set: Methionine synthase route by cobalamin dependence (One Or More)

Cobalamin-dependent MetH routeReactionmeth_variant

Annotons

Cobalamin-dependent methionine synthase

meth_activity

Participant: Family: Methionine synthase family

Family:

Methionine synthase familyPANTHER:PTHR45833

Representative Members: PSEPK MetHUniProtKB:Q88KB5

Function

methionine synthase activityGO:0008705

Substrates: 5-methyltetrahydrofolateCHEBI:18608 L-homocysteineCHEBI:58199

Products: tetrahydrofolateCHEBI:57453 L-methionineCHEBI:57844

Regenerates methionine using cobalamin and 5-methyltetrahydrofolate.

Cobalamin-independent MetE routeReactionmete_variant

Annotons

Cobalamin-independent methionine synthase

mete_activity

Participant: Family: Cobalamin-independent methionine synthase family

Family:

Cobalamin-independent methionine synthase familyPANTHER:PTHR30519

Representative Members: PSEPK MetE candidateUniProtKB:Q88JF1

Function

5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activityGO:0003871

Regenerates methionine without a cobalamin cofactor.