GapMind for Amino acid biosynthesis


L-methionine biosynthesis in Dyella japonica UNC79MFTsu3.2

Best path

asp-kinase, asd, hom, metA, metB, metC?, 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 (13 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate Class of gap
asp-kinase aspartate kinase N515DRAFT_4002  
asd aspartate semi-aldehyde dehydrogenase N515DRAFT_0109  
hom homoserine dehydrogenase N515DRAFT_0577 N515DRAFT_4364  
metA homoserine O-succinyltransferase N515DRAFT_2885 N515DRAFT_4362  
metB cystathionine gamma-synthase N515DRAFT_4363 N515DRAFT_4305  
metC? cystathionine beta-lyase N515DRAFT_4305 N515DRAFT_4363 diverged
metH* vitamin B12-dependent methionine synthase N515DRAFT_0495 with N515DRAFT_0494  
B12-reactivation-domain MetH reactivation domain N515DRAFT_0495  
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 N515DRAFT_0576  
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  
metE vitamin B12-independent methionine synthase N515DRAFT_1630  
metX homoserine O-acetyltransferase N515DRAFT_2885 N515DRAFT_4362  
metY O-acetylhomoserine sulfhydrylase N515DRAFT_4305 N515DRAFT_4363  
metZ O-succinylhomoserine sulfhydrylase N515DRAFT_4305 N515DRAFT_4363  
ramA ATP-dependent reduction of co(II)balamin  
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains  
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.



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 the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, 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