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.

Reusable boundary: this module is a route-choice template, with homoserine acylation, sulfur incorporation, and terminal methylation modeled as required steps that may be satisfied by alternatives. The PSEPK instantiation appears satisfiable through Pseudomonas-style O-succinylhomoserine direct sulfhydrylation (metXS plus metZ) and terminal metH, with metB plus PP_4348 as a plausible secondary trans-sulfuration route. metE is a predicted compact single-barrel cobalamin-independent MetE candidate that still lacks direct KT2440 biochemical evidence. PP_2528, PP_4594, and PP_4637 should be treated as route/paralog-ambiguous unless gene-level evidence establishes physiological methionine-biosynthesis roles.