As text, or see rules and steps
# L-lactate degradation in GapMind is based on L-lactate dehydrogenases or oxidases. # E. coli GlcA (Q46839) is similar to LctP and is reported to transport both L- and D-lactate. # PS417_24105 (GFF4172) is important only for D-lactate utilization but is closely related to AO356_07550 # and could be an L-lactate transporter as well. # SO_1522 (Q8EGS2) and Psest_0955 (L0GFN1) probably transport both isomers. # Bacillus subtilis LutP (uniprot:P71067) is an L-lactate transporter. lctP L-lactate:H+ symporter LctP or LidP curated:SwissProt::P33231 curated:SwissProt::P71067 curated:reanno::pseudo5_N2C3_1:AO356_07550 curated:TCDB::Q46839 ignore:reanno::WCS417:GFF4712 uniprot:Q8EGS2 uniprot:L0GFN1 curated:SwissProt::P71067 # Transporters were identified using # query: transporter:L-lactate:(S)-lactate:D,L-lactic # and prokaryotic lactate transporters were examined as well. # Exchangers for lactate/citrate or lactate/malate were ignored. L-lactate-transport: lctP SfMCT L-lactate transporter SfMCT curated:SwissProt::A0LNN5 L-lactate-transport: SfMCT larD D,L-lactic acid transporter LarD curated:SwissProt::F9UST3 curated:SwissProt::F9UMX3 L-lactate-transport: larD mctP D,L-lactic acid transporter MctP curated:TCDB::Q8VM88 curated:SwissProt::Q1M7A2 L-lactate-transport: mctP # 2-component L-lactate transporter from Shewanella loihica PV-4. A # related system in Shewanella amazonesnsis SB2B is also probably a # L-lactate transporter (SB2B cannot utilize D-lactate), but its # specificity is not proven, so it is marked ignore. Shew_2731 L-lactate:Na+ symporter, large component curated:reanno::PV4:5209923 ignore:reanno::SB2B:6937353 Shew_2732 L-lactate:Na+ symporter, small component curated:reanno::PV4:5209924 ignore:reanno::SB2B:6937352 L-lactate-transport: Shew_2731 Shew_2732 # TLBP_THET8 / Q5SK82 is thought to be the periplasmic # substrate-binding component of a TRAP system, and has been shown to # bind calcium L-lactate (the calcium can be replaced by other # divalent ions; PMID:19631222). However the other components of this # putative TRAP system have not been studied. # F8SVK1 (TC 2.A.1.6.11) seems to be a weak lactate transporter, so ignore # A0A0H3W5K4/I3VSF1 appears to be misannotated in BRENDA L-LDH L-lactate dehydrogenase EC:1.1.2.3 EC:1.1.1.27 ignore:BRENDA::A0A0H3W5K4 ignore:BRENDA::I3VSF1 # Various L-lactate dehydrogenases are known, with different numbers of subunits; these all form pyruvate. L-lactate-degradation: L-LDH # A three-component L-lactate dehydrogenase LldEFG was described in Shewanella oneidensis # (see PMID:19196979). # A related system in Burkholderia phytofirmans PsJN is also required for L-lactate utilization; # the lldEF subunits are quite similar but the lldG is diverged. # LldE = SO_1520 or BPHYT_RS26975 lldE L-lactate dehydrogenase, LldE subunit uniprot:Q8EGS4 uniprot:B2TBW0 # LldF = SO_1519 or BPHYT_RS26970 lldF L-lactate dehydrogenase, LldF subunit uniprot:Q8EGS5 uniprot:B2TBY8 # LldG = SO_1518 or BPHYT_RS26965 lldG L-lactate dehydrogenase, LldG subunit uniprot:Q8EGS6 uniprot:B2TBY7 L-lactate-degradation: lldE lldF lldG # A three-component L-lactate dehydrogenase LutABC was described in # Bacillus subtilis (PMC3347220, PMC2668416). # Although LutABC does not seem to have been studied biochemically, # it is required for L-lactate utilization, and induced during # growth on L-lactate, and is distantly related to lldEFG. # The related system from B. cereus has also been studied. # Based on fitness data, similar systems were identified in # Cupriavidus basilensis FW507-4G11 (lutA = RR42_RS21295; lutB = RR42_RS21285; lutC = RR42_RS21290) # and Marinobacter adhaerens HP15 (lutA = HP15_4088, lutB = HP15_4089, lutC = HP15_4090). lutA L-lactate dehydrogenase, LutA subunit curated:SwissProt::O07020 curated:SwissProt::Q81GA5 uniprot:A0A0C4YIN5 uniprot:E4PLR5 lutB L-lactate dehydrogenase, LutB subunit curated:SwissProt::O07021 curated:SwissProt::Q81GA4 uniprot:A0A0C4Y8G6 uniprot:E4PLR6 lutC L-lactate dehydrogenase, LutC subunit curated:SwissProt::O32259 curated:SwissProt::Q81GA3 uniprot:A0A0C4YFN9 uniprot:E4PLR7 L-lactate-degradation: lutA lutB lutC # In Desulfovibrio vulgaris Hildenborough, a 2-component L-lactate dehydrogenase (DVU3032 and DVU3033) was identified # (PMC4481167). Genome-wide fitness data did not identify any additional components. # DVU3033 appears to be a fusion of lutA and lutB, and DVU3032 is distantly related to lutC DVU3033 L-lactate dehydrogenase, fused LutA/LutB components uniprot:Q726S3 DVU3032 L-lactate dehydrogenase, LutC-like component uniprot:Q726S4 L-lactate-degradation: DVU3033 DVU3032 # L-lactate oxidase (EC 1.13.12.4, formerly 1.1.3.2) oxidizes L-lactate to acetate # and CO2 under aerobic conditions. Some of these enzymes produce # pyruvate (and hydroxgen peroxide) instead, but are still given this # EC number. Either way, the acetate can be used for growth. # However this enzyme is # mostly found in fermentative bacteria, so its role could be # to detoxify the accumulated lactate. # Since L-lactate is a (S)-2-hydroxy-acid, ignore any similarities to # (S)-2-hydroxy-acid oxidases (1.1.3.15) lctO L-lactate oxidase or 2-monooxygenase EC:1.13.12.4 EC:1.1.3.2 ignore_other:1.1.3.15 # acetyl-CoA synthase or acetate kinase and phosphate acetyltransferase import ethanol.steps:acs ackA pta # Or, after L-lactate oxidase (lctO) forms acetate, the acetate is activated to acetyl-CoA. L-lactate-degradation: lctO acs L-lactate-degradation: lctO ackA pta all: L-lactate-transport L-lactate-degradation
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:
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