GapMind for Amino acid biosynthesis

 

L-methionine biosynthesis in Bacteroides thetaiotaomicron VPI-5482

Best path

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

Also see fitness data for the top candidates

Rules

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 (12 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase BT2403 BT1375
asd aspartate semi-aldehyde dehydrogenase BT3636
hom homoserine dehydrogenase BT2403
metX homoserine O-acetyltransferase BT2413
metY O-acetylhomoserine sulfhydrylase BT2387 BT1923
metH* vitamin B12-dependent methionine synthase BT0180 with BT0249
B12-reactivation-domain MetH reactivation domain BT0249 BT0342
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
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
metA homoserine O-succinyltransferase BT2413
metB cystathionine gamma-synthase BT1923 BT2387
metC cystathionine beta-lyase BT4138 BT1398
metE vitamin B12-independent methionine synthase
metZ O-succinylhomoserine sulfhydrylase BT2387 BT1923
ramA ATP-dependent reduction of co(II)balamin
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains BT0340 BT0180
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 against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer. 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. 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 the paper from 2019 on GapMind for amino acid biosynthesis, or view the source code, or see changes to Amino acid biosynthesis since the publication.

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