GapMind for Amino acid biosynthesis

 

L-methionine biosynthesis in Thiomicrospira microaerophila ASL8-2

Best path

asp-kinase, asd, hom, metA, metB, metC, metH, B12-reactivation-domain

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.

27 steps (15 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase NA59_RS06170
asd aspartate semi-aldehyde dehydrogenase NA59_RS02600
hom homoserine dehydrogenase NA59_RS00230 NA59_RS06170
metA homoserine O-succinyltransferase NA59_RS08750
metB cystathionine gamma-synthase NA59_RS02555 NA59_RS04485
metC cystathionine beta-lyase NA59_RS13295 NA59_RS02555
metH vitamin B12-dependent methionine synthase NA59_RS08555
B12-reactivation-domain MetH reactivation domain NA59_RS08555
Alternative steps:
asd-S-ferredoxin L-aspartate semialdehyde sulfurtransferase, NIL/ferredoxin component
asd-S-perS L-aspartate semialdehyde sulfurtransferase, persulfide-forming component
asd-S-transferase L-aspartate semialdehyde sulfurtransferase, persulfide component
hom_kinase homoserine kinase NA59_RS13220 NA59_RS03705
mesA Methylcobalamin:homocysteine methyltransferase MesA
mesB Methylcobalamin:homocysteine methyltransferase MesB
mesC Methylcobalamin:homocysteine methyltransferase MesC
mesD oxygen-dependent methionine synthase, methyltransferase component MesD
mesX oxygen-dependent methionine synthase, putative oxygenase component MesX
metE vitamin B12-independent methionine synthase NA59_RS08475
metX homoserine O-acetyltransferase NA59_RS08750
metY O-acetylhomoserine sulfhydrylase NA59_RS04485 NA59_RS02555
metZ O-succinylhomoserine sulfhydrylase NA59_RS02555 NA59_RS04485
ramA ATP-dependent reduction of co(II)balamin
split_metE_1 vitamin B12-independent methionine synthase, folate-binding component
split_metE_2 vitamin B12-independent methionine synthase, catalytic component NA59_RS08475
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains NA59_RS08555
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 Jul 25 2024. The underlying query database was built on Jul 25 2024.

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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