GapMind for Amino acid biosynthesis


L-methionine biosynthesis in Tistlia consotensis USBA 355

Best path

asp-kinase, asd, hom, metX, metY, metH*, B12-reactivation-domain


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.

27 steps (18 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase B9O00_RS15090
asd aspartate semi-aldehyde dehydrogenase B9O00_RS08315
hom homoserine dehydrogenase B9O00_RS11055 B9O00_RS15090
metX homoserine O-acetyltransferase B9O00_RS02195 B9O00_RS16385
metY O-acetylhomoserine sulfhydrylase B9O00_RS17905 B9O00_RS14855
metH* vitamin B12-dependent methionine synthase B9O00_RS30280 with B9O00_RS34200
B12-reactivation-domain MetH reactivation domain B9O00_RS30280
Alternative steps:
asd-S-ferredoxin reductive sulfuration of L-aspartate semialdehyde, ferredoxin component
asd-S-perS putative persulfide forming protein B9O00_RS10355
asd-S-transferase sulfuration of L-aspartate semialdehyde, persulfide component
hom_kinase homoserine kinase B9O00_RS03430 B9O00_RS14965
mesA Methylcobalamin:homocysteine methyltransferase MesA
mesB Methylcobalamin:homocysteine methyltransferase MesB
mesC Methylcobalamin:homocysteine methyltransferase MesC
mesD oxygen-dependent methionine synthase, methyltransferase component MesD B9O00_RS01245
mesX oxygen-dependent methionine synthase, putative oxygenase component MesX
metA homoserine O-succinyltransferase B9O00_RS02195 B9O00_RS16385
metB cystathionine gamma-synthase B9O00_RS09255 B9O00_RS10510
metC cystathionine beta-lyase B9O00_RS10510 B9O00_RS06685
metE vitamin B12-independent methionine synthase
metZ O-succinylhomoserine sulfhydrylase B9O00_RS09255 B9O00_RS10510
ramA ATP-dependent reduction of co(II)balamin B9O00_RS10440
split_metE_1 vitamin B12-independent methionine synthase, folate-binding component
split_metE_2 vitamin B12-independent methionine synthase, catalytic component
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains B9O00_RS10405 B9O00_RS30280
split_metH_2 Methionine synthase component, methyltransferase domain B9O00_RS20360
split_metH_3 Methionine synthase component, pterin-binding domain B9O00_RS10435

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Apr 09 2024. The underlying query database was built on Apr 09 2024.



Related tools

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