L-methionine biosynthesis (from homoserine)

De novo biosynthesis of L-methionine from L-homoserine, modelled as a species-agnostic pathway template with alternative routes at three steps, so the same logic can be evaluated across genomes (a eukaryote-to-prokaryote test of the module satisfiability engine). Homoserine is first activated by acylation, for which bacteria use either an O-succinyltransferase (metA) or an O-acetyltransferase (metX). Sulfur is then incorporated to give homocysteine by one of two routes: trans-sulfuration (cystathionine gamma-synthase metB plus cystathionine beta-lyase metC, drawing sulfur from cysteine) or direct sulfhydrylation (an O-acyl-homoserine sulfhydrylase, metY/metZ, using free sulfide in a single step). Finally homocysteine is methylated to methionine by either the cobalamin-independent synthase (metE) or the cobalamin-dependent synthase (metH). Because every step has alternatives, no single enzyme is universally required; an organism makes methionine if it encodes at least one option at each of the three steps. This mirrors GapMind-style pathway reconstruction: the template defines steps and route alternatives, and a per-genome oracle decides which candidates are present.

MODULE:methionine_biosynthesisDRAFTMetabolic Pathwaymodules/methionine_biosynthesis.yaml
methionine biosynthesisGO:0071265
GO:0071265
L-methionine biosynthetic process
Module grounded in the GO biological-process term for L-methionine biosynthesis.
KEGG:map00270
Cysteine and methionine metabolism
Step alternatives (metA/metX; trans-sulfuration vs direct sulfhydrylation; metE/metH) follow the KEGG/MetaCyc methionine biosynthesis routes; per-genome presence is resolved via KEGG Orthology (see oracle).
12Nodes
5Parts
3Variant Sets
6Variants
7Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

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

Leaf nodes lacking representative members

every leaf node grounds to a representative protein.

Template conformance

every declared conforms_to bundle matches its template motif.

Gene-review completeness (0/0 grounded genes reviewed)

No concrete UniProt-grounded genes in this module.

Details

L-methionine biosynthesisMetabolic Pathwaymethionine_biosynthesis
methionine biosynthesisGO:0071265

Species-agnostic GapMind-style template. Steps are grounded by gene symbol and GO molecular function; the authoritative per-genome step candidates are KEGG Orthology ids held by the oracle (metA=K00651, metX=K00641, metB=K01739, metC=K01760, metY=K01740, metE=K00549, metH=K00548). See modules/experimental/gluconeogenesis-context/kegg_oracle.py and resolve_genomes.py for per-genome route resolution and gap detection.

Connections

Part 1: acylation of homoserine (succinyl or acetyl)
Homoserine activation by acylationReactionacylation
Variant set: Homoserine acyltransferase by acyl donor (One Or More)
O-succinyltransferase (metA)ReactionmetA_variant

Annotons

metA: homoserine O-succinyltransferase
metA_activity
Participant: Gene: metA (homoserine O-succinyltransferase)
Gene:
metA (homoserine O-succinyltransferase)

Function

homoserine O-succinyltransferase activityGO:0008899

Activates homoserine to O-succinyl-L-homoserine.

O-acetyltransferase (metX)ReactionmetX_variant

Annotons

metX: homoserine O-acetyltransferase
metX_activity
Participant: Gene: metX (homoserine O-acetyltransferase)
Gene:
metX (homoserine O-acetyltransferase)

Function

homoserine O-acetyltransferase activityGO:0004414

Activates homoserine to O-acetyl-L-homoserine.

Part 2: sulfur incorporation to homocysteine (trans-sulfuration or direct)
Sulfur incorporation to homocysteineMetabolic Pathwaysulfur_incorporation
Variant set: Sulfur-incorporation route by sulfur source (One Or More)
Trans-sulfuration (metB + metC)Metabolic Pathwaytrans_sulfuration

Two enzymes, drawing sulfur from cysteine via cystathionine.

Part 1: cystathionine formation
Cystathionine gamma-synthaseReactionmetB_node

Annotons

metB: cystathionine gamma-synthase
metB_activity
Participant: Gene: metB (cystathionine gamma-synthase)
Gene:
metB (cystathionine gamma-synthase)

Function

cystathionine gamma-synthase activityGO:0003962
Part 2: cystathionine cleavage to homocysteine
Cystathionine beta-lyaseReactionmetC_node

Annotons

metC: cystathionine beta-lyase
metC_activity
Participant: Gene: metC (cystathionine beta-lyase)
Gene:
metC (cystathionine beta-lyase)

Function

cysteine-S-conjugate beta-lyase activityGO:0047804
Direct sulfhydrylation (metY)Reactiondirect_sulfhydrylation

One enzyme, using free sulfide on O-acyl-homoserine.

Annotons

metY: O-acylhomoserine sulfhydrylase
metY_activity
Participant: Gene: metY (O-acetylhomoserine sulfhydrylase)
Gene:
metY (O-acetylhomoserine sulfhydrylase)

Function

O-acetylhomoserine aminocarboxypropyltransferase activityGO:0003961
Part 3: methylation of homocysteine to methionine (cobalamin-independent or -dependent)
Homocysteine methylation to methionineReactionmethylation
Variant set: Methionine synthase by cobalamin dependence (One Or More)
Cobalamin-independent synthase (metE)ReactionmetE_variant

Annotons

metE: cobalamin-independent methionine synthase
metE_activity
Participant: Gene: metE (cobalamin-independent methionine synthase)
Gene:
metE (cobalamin-independent methionine synthase)

Function

5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activityGO:0003871
Cobalamin-dependent synthase (metH)ReactionmetH_variant

Annotons

metH: cobalamin-dependent methionine synthase
metH_activity
Participant: Gene: metH (cobalamin-dependent methionine synthase)
Gene:
metH (cobalamin-dependent methionine synthase)

Function

methionine synthase activityGO:0008705