GapMind for Amino acid biosynthesis


L-methionine biosynthesis in Pseudomonas fluorescens FW300-N2E2

Best path

asp-kinase, asd, hom, metA, metZ, metH, B12-reactivation-domain

Also see fitness data for the top candidates


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.

24 steps (14 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Pf6N2E2_5676
asd aspartate semi-aldehyde dehydrogenase Pf6N2E2_67 Pf6N2E2_68
hom homoserine dehydrogenase Pf6N2E2_3143 Pf6N2E2_4963
metA homoserine O-succinyltransferase Pf6N2E2_4597
metZ O-succinylhomoserine sulfhydrylase Pf6N2E2_77 Pf6N2E2_4958
metH vitamin B12-dependent methionine synthase Pf6N2E2_2068
B12-reactivation-domain MetH reactivation domain Pf6N2E2_2068
Alternative steps:
asd-S-ferredoxin reductive sulfuration of L-aspartate semialdehyde, ferredoxin component
asd-S-perS putative persulfide forming protein
asd-S-transferase sulfuration of L-aspartate semialdehyde, persulfide component
hom_kinase homoserine kinase Pf6N2E2_4164 Pf6N2E2_3755
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
metB cystathionine gamma-synthase Pf6N2E2_4958 Pf6N2E2_77
metC cystathionine beta-lyase Pf6N2E2_1491 Pf6N2E2_4958
metE vitamin B12-independent methionine synthase Pf6N2E2_5472
metX homoserine O-acetyltransferase Pf6N2E2_4597
metY O-acetylhomoserine sulfhydrylase Pf6N2E2_77 Pf6N2E2_4958
ramA ATP-dependent reduction of co(II)balamin
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains Pf6N2E2_2068
split_metH_2 Methionine synthase component, methyltransferase domain
split_metH_3 Methionine synthase component, pterin-binding domain

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 Aug 03 2021. The underlying query database was built on Aug 03 2021.



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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