GapMind for Amino acid biosynthesis


Definition of L-methionine biosynthesis

As rules and steps, or see full text


Overview: Methionine biosynthesis in GapMind is based on MetaCyc pathways L-methionine biosynthesis I via O-succinylhomoserine and cystathionine (link), II via O-phosphohomoserine and cystathionine (link), III via O-acetylhomoserine (link), or IV with reductive sulfhydrylation of aspartate semialdehyde (link). These pathways vary in how aspartate semialdehyde is reduced and sulfhydrylated to homocysteine. GapMind does not represent the formation of the methyl donors for methionine synthase, such as 5-methyltetrahydrofolate or methyl corrinoid proteins.


asp-kinase: aspartate kinase

asd: aspartate semi-aldehyde dehydrogenase

hom: homoserine dehydrogenase

metA: homoserine O-succinyltransferase

metX: homoserine O-acetyltransferase

hom_kinase: homoserine kinase

metB: cystathionine gamma-synthase

metC: cystathionine beta-lyase

metY: O-acetylhomoserine sulfhydrylase

metZ: O-succinylhomoserine sulfhydrylase

metE: vitamin B12-independent methionine synthase

metH: vitamin B12-dependent methionine synthase

split_metH_1: Methionine synthase component, B12 binding and B12-binding cap domains

split_metH_2: Methionine synthase component, methyltransferase domain

split_metH_3: Methionine synthase component, pterin-binding domain

B12-reactivation-domain: MetH reactivation domain

ramA: ATP-dependent reduction of co(II)balamin

asd-S-transferase: sulfuration of L-aspartate semialdehyde, persulfide component

asd-S-ferredoxin: reductive sulfuration of L-aspartate semialdehyde, ferredoxin component

asd-S-perS: putative persulfide forming protein

mesA: Methylcobalamin:homocysteine methyltransferase MesA

mesB: Methylcobalamin:homocysteine methyltransferase MesB

mesD: oxygen-dependent methionine synthase, methyltransferase component MesD

mesX: oxygen-dependent methionine synthase, putative oxygenase component MesX



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About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory