GapMind for Amino acid biosynthesis


L-methionine biosynthesis in Pseudomonas fluorescens FW300-N1B4

Manual classification of gap: spurious
Rationale: By comparing the published assembly to alternate assemblies, we identified a region that was missing. It included an open reading frame with 84% identity to METZ_PSEAE.

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 (14 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Pf1N1B4_3451
asd aspartate semi-aldehyde dehydrogenase Pf1N1B4_11 Pf1N1B4_10
hom homoserine dehydrogenase Pf1N1B4_3013
metA homoserine O-succinyltransferase Pf1N1B4_2338
metB? cystathionine gamma-synthase Pf1N1B4_4890 Pf1N1B4_4430
metC cystathionine beta-lyase Pf1N1B4_4430 Pf1N1B4_4890
metH vitamin B12-dependent methionine synthase Pf1N1B4_5661
B12-reactivation-domain MetH reactivation domain Pf1N1B4_5661
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 Pf1N1B4_1873 Pf1N1B4_1538
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 Pf1N1B4_783
metX? homoserine O-acetyltransferase Pf1N1B4_2338
metY? O-acetylhomoserine sulfhydrylase Pf1N1B4_4890 Pf1N1B4_4430
metZ? O-succinylhomoserine sulfhydrylase Pf1N1B4_4890 Pf1N1B4_4430
ramA? ATP-dependent reduction of co(II)balamin
split_metH_1? Methionine synthase component, B12 binding and B12-binding cap domains Pf1N1B4_5661
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