As text, or see rules and steps
# After uptake, acetate can be converted to acetyl-CoA by acs or by # ackA and pta, see MetaCyc's superpathway of acetate # utilization and formation (metacyc:ACETATEUTIL-PWY). # Acetyl-CoA is a central metabolic intermediate, so further reactions # are not represented in GapMind. Acetyl-CoA may be catabolized by the TCA # cycle or, in strict anaerobes, by the Wood-Ljungdahl pathway. If the # TCA cycle is used, then intermediates need to be replenished # by anaplaerotic reactions such as the glyoxylate cycle or the # ethylmalonyl-CoA pathway. actP cation/acetate symporter ActP curated:SwissProt::P32705 curated:SwissProt::Q8NS49 curated:TCDB::D5APM1 curated:TCDB::D5AU53 # Transporters were identified using # query: transporter:acetate:acetic. acetate-transport: actP # Ignore the poorly characterized protein GPR1_YARLI (uniprot:P41943) from Yarrowia lipolytica ady2 acetate permease Ady2 curated:SwissProt::P25613 curated:SwissProt::Q5B2K4 ignore:SwissProt::P41943 acetate-transport: ady2 patA Acetate transporter PatA curated:SwissProt::A0A075TRL0 curated:SwissProt::A1CFK8 acetate-transport: patA # Added the singleton Deh4p (M1Q159) from Dehalococcoides mccartyi, which has the same domain deh acetate/haloacid transporter curated:TCDB::F8SVK1 curated:TCDB::Q7X4L6 curated:TCDB::M1Q159 acetate-transport: deh satP acetate/proton symporter satP curated:SwissProt::P0AC98 acetate-transport: satP SLC5A8 actetate:Na+ symporter SLC5A8 curated:SwissProt::Q8N695 acetate-transport: SLC5A8 # TC 1.A.14.2.2 reports that E. coli yhbL is an acetate transporter, and cites a personal communication # from M. Inouye. ybhL acetate uptake transporter YbhL curated:TCDB::P0AAC4 acetate-transport: ybhL # A mutant in P. chlororaphis is reported to be defective in acetate utilization, implying uptake. # Fitness data for various strains of P. fluorescens did not indicate this, but uptake could be redundant; # for the ortholog in P. aeruginosa (uniprot:Q9I4F5), acetate does not seem to have been considered as a potential substrate dctA organic acid/proton symporter DctA curated:TCDB::Q848I3 ignore:SwissProt::Q9I4F5 ignore:reanno::pseudo5_N2C3_1:AO356_18980 acetate-transport: dctA # Ignored efflux systems, acyl-CoA transporter (annotated as actetate non-utilizing), # non-specific chloride channel protein, and # citrate:acetate antiporter. import ethanol.steps:acs ackA pta all: acetate-transport acs all: acetate-transport ackA pta
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:
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.
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