GapMind for Amino acid biosynthesis


L-methionine biosynthesis in Sulfurihydrogenibium azorense Az-Fu1

Best path

asp-kinase, asd, hom, hom_kinase, metB?, metC?, metE


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 (10 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate Known gap?
asp-kinase aspartate kinase SULAZ_RS07315  
asd aspartate semi-aldehyde dehydrogenase SULAZ_RS08120  
hom homoserine dehydrogenase SULAZ_RS02015 SULAZ_RS07315  
hom_kinase homoserine kinase SULAZ_RS02060  
metB? cystathionine gamma-synthase known gap
metC? cystathionine beta-lyase SULAZ_RS01475 known gap
metE vitamin B12-independent methionine synthase SULAZ_RS03890  
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 SULAZ_RS03260  
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  
metA homoserine O-succinyltransferase  
metH vitamin B12-dependent methionine synthase SULAZ_RS03260  
metX homoserine O-acetyltransferase  
metY O-acetylhomoserine sulfhydrylase  
metZ O-succinylhomoserine sulfhydrylase  
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 SULAZ_RS03890  
split_metH_1 Methionine synthase component, B12 binding and B12-binding cap domains SULAZ_RS03260  
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 Apr 09 2024. The underlying query database was built on Apr 09 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