GapMind for Amino acid biosynthesis

 

L-methionine biosynthesis in Dinoroseobacter shibae DFL-12

Best path

asp-kinase, asd, hom, metX, metY, split_metH_1, split_metH_2, split_metH_3, ramA

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 (15 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Dshi_2061
asd aspartate semi-aldehyde dehydrogenase Dshi_3240
hom homoserine dehydrogenase Dshi_2273
metX homoserine O-acetyltransferase Dshi_1593
metY O-acetylhomoserine sulfhydrylase Dshi_0793 Dshi_2410
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains Dshi_1073
split_metH_2 Methionine synthase component, methyltransferase domain Dshi_1074
split_metH_3 Methionine synthase component, pterin-binding domain Dshi_1677
ramA ATP-dependent reduction of co(II)balamin Dshi_1680
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
B12-reactivation-domain MetH reactivation domain
hom_kinase homoserine kinase Dshi_1609
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 Dshi_1593
metB cystathionine gamma-synthase Dshi_1002 Dshi_2410
metC cystathionine beta-lyase Dshi_0178 Dshi_1002
metE vitamin B12-independent methionine synthase
metH* vitamin B12-dependent methionine synthase Dshi_1677 with Dshi_1074
metZ O-succinylhomoserine sulfhydrylase Dshi_2410 Dshi_0793

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