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_cycleCOMPLETEMetabolic 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.
file:genes/ECOLI/pfs/pfs-ai-review.yaml
ECOLI pfs gene review
The completed E. coli pfs review grounds MtnN/Pfs as the cytosolic SAH and 5'-methylthioadenosine nucleosidase that supplies S-ribosylhomocysteine to LuxS.
file:genes/ECOLI/luxS/luxS-ai-review.yaml
ECOLI luxS gene review
The completed E. coli luxS review grounds LuxS as the cytosolic S-ribosylhomocysteine lyase that releases L-homocysteine for methionine regeneration.
11Nodes
6Parts
2Variant Sets
4Variants
7Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

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:

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

6 gene-function check(s) reflected in core functions · 0 conflict(s) · 3 evidence or coverage gap(s) (13 comparison(s))

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

AnnotonParticipantFunctionAssessment
metk_activity PSEPK MetK
UniProtKB:Q88D60
Family Representative 		methionine adenosyltransferase activity
GO:0004478 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sam_methyltransferase_activity ANY_WITH_FUNCTION
Gene 		SAM-dependent methyltransferase activity
GO:0008757 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
ahcy_activity PSEPK AhcY
UniProtKB:A0A140FWS3
Family Representative 		adenosylhomocysteinase activity
GO:0004013 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtnn_activity Escherichia coli K-12 MtnN/Pfs
UniProtKB:P0AF12
Family Representative 		adenosylhomocysteine nucleosidase activity
GO:0008782 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
luxs_activity Escherichia coli K-12 LuxS
UniProtKB:P45578
Family Representative 		S-ribosylhomocysteine lyase activity
GO:0043768 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
meth_activity PSEPK MetH
UniProtKB:Q88KB5
Family Representative 		methionine synthase activity
GO:0008705 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mete_activity PSEPK MetE candidate
UniProtKB:Q88JF1
Family Representative 		5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity
GO:0003871 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
metk_activity S-adenosylmethionine synthetase family
PANTHER:PTHR11964
Family 		methionine adenosyltransferase activity
GO:0004478 		Family Supported
Family review supports GO:0004478 FAMILY_WIDE. Asserted by methionine_cycle, sam_cycle and bacterial_methionine_cycle; accepted by SAM1, SAM2, sam1, MAT1A, P. putida MetK and the poplar SAMS paralogs.
ahcy_activity Adenosylhomocysteinase family
PANTHER:PTHR23420
Family 		adenosylhomocysteinase activity
GO:0004013 		Family Scope Restricted
GO:0004013 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Catalytic subfamilies only. methionine_cycle, sam_cycle and bacterial_methionine_cycle select the base family, which also takes in AHCYL1/2.
mtnn_activity MtnN/Pfs nucleosidase family
PANTHER:PTHR46832
Family 		adenosylhomocysteine nucleosidase activity
GO:0008782 		Family Scope Restricted
GO:0008782 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by bacterial_methionine_cycle; accepted by E. coli pfs.
luxs_activity LuxS family
PANTHER:PTHR35799
Family 		S-ribosylhomocysteine lyase activity
GO:0043768 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR35799.
meth_activity Methionine synthase family
PANTHER:PTHR45833
Family 		methionine synthase activity
GO:0008705 		Family Supported
Family review supports GO:0008705 FAMILY_WIDE. Asserted by methionine_cycle, homocysteine_metabolism and bacterial_methionine_cycle; accepted by MTR and P. putida metH.
mete_activity Cobalamin-independent methionine synthase family
PANTHER:PTHR30519
Family 		5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity
GO:0003871 		Family Supported
Family review supports GO:0003871 FAMILY_WIDE. Asserted by methionine_cycle and bacterial_methionine_cycle; accepted by MET6, met26 and P. putida MetE. The truncated PP_4637 is left UNDECIDED by its review.

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

6 complete review(s) · 2 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
ahcY A0A140FWS3 ✓ ✓ ✗
luxS P45578 ✓ ✓ ✗
metE Q88JF1 ✓ ✓ ✓
metH Q88KB5 ✓ ✓ ✓
metK Q88D60 ✓ ✓ ✗
pfs P0AF12 ✓ ✓ ✗

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.
Complete SAH processing supplies homocysteine for remethylation.
Remethylation regenerates methionine for another cycle.
Part 1: S-adenosyl-L-methionine synthesis
Methionine adenosylation to SAMReactionsam_synthesis

Annotons

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

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.