Bacterial dimethylglycine and sarcosine catabolism

A reusable two-step bacterial module for sequential N-demethylation of dimethylglycine to sarcosine and then glycine. The first reaction may be performed by a DgcA-like flavoprotein that reduces a membrane-associated DgcB-like iron-sulfur ferredoxin. Reduced DgcB is proposed to pass reducing equivalents to a pathway-associated heterodimeric ETF. The second reaction may use a tetrahydrofolate-coupled SoxBDAG heterotetramer or a monomeric sarcosine oxidase. Upstream glycine-betaine demethylation and downstream glycine cleavage or serine conversion are outside the module boundary.

MODULE:bacterial_dimethylglycine_sarcosine_catabolismDRAFTCONCRETEMetabolic Pathwaymodules/bacterial_dimethylglycine_sarcosine_catabolism.yaml
PMID:17951379
Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism.
Mutant growth and isotope-tracing experiments support DgcAB-dependent dimethylglycine-to-sarcosine and SoxBDAG-dependent sarcosine-to-glycine conversion in Pseudomonas aeruginosa.
Similar experiments showed that strains with mutations in the dgcAB (PA5398-PA5399) genes, which exhibit homology to genes that encode other enzymes with demethylase activity, are required for the conversion of DMG to sarcosine.
PMID:35266867
Creatine utilization as a sole nitrogen source in Pseudomonas putida KT2440 is transcriptionally regulated by CahR.
The KT2440 creatine-utilization study identifies SoxBDAG as pathway background for conversion of sarcosine to glycine and formaldehyde.
sarcosine is then converted to glycine and formaldehyde by the tetrameric sarcosine oxidase (SoxBDAG)
PMID:32631860
Role of N,N-Dimethylglycine and Its Catabolism to Sarcosine in Chromohalobacter salexigens DSM 3043.
Biochemical analysis directly establishes DdhC as an FAD-containing, NAD(P)-using dimethylglycine dehydrogenase, while disruption of the adjacent ferredoxin and ETF genes supports their pathway participation. The ordered DdhC-to-ferredoxin-to-ETF relay is a mechanistic inference.
gene disruption and complementation assays indicated that the csal_0990, csal_0991, csal_0992, and csal_0993 genes are responsible for DMG degradation to sarcosine.
PMID:9185627
Folate utilization by monomeric versus heterotetrameric sarcosine oxidases.
Biochemical comparison shows that heterotetrameric sarcosine oxidases efficiently couple the one-carbon unit to tetrahydrofolate, whereas monomeric enzymes predominantly release formaldehyde.
The results show that only the heterotetrameric sarcosine oxidases can use tetrahydrofolates as substrates
PMID:15946648
Crystal structure of heterotetrameric sarcosine oxidase from Corynebacterium sp. U-96.
The structure assigns NAD and folate binding to SoxA, FAD and FMN to SoxB, and a Cys3His-bound zinc atom to SoxD.
The alpha subunit is composed of two domains, contains NAD(+), and binds folinic acid. The beta subunit contains dimethylglycine, FAD, and FMN, and these flavins are approximately 10A apart.
UniProtKB:Q1QYW1
Reviewed DgcA-like bacterial dimethylglycine dehydrogenase
Q1QYW1 is the directly characterized DgcA-like bacterial dehydrogenase. Its assignment to a relay with Q1QYW0 and ETF is based on the genetically required four-gene locus and the mechanism proposed for that system.
UniProtKB:Q1QYW0
Reviewed DgcB-like membrane-anchored ferredoxin
Q1QYW0 is a reviewed membrane-anchored ferredoxin and a genetically required member of the Q1QYW1-associated degradation locus; direct electron transfer between the purified proteins has not been shown.
UniProtKB:Q50LF0
Reviewed tetrameric sarcosine oxidase alpha subunit
Q50LF0 and its reviewed Corynebacterium partner entries ground the tetrahydrofolate-coupled SoxABDG complex.
UniProtKB:P40873
Reviewed monomeric sarcosine oxidase
P40873 grounds the alternative single-chain sarcosine oxidase.

The PSEPK DgcAB-ETF system has strong pathway-level orthology and conserved locus evidence, but the exact KT2440 proteins have not been reconstituted biochemically. Electron flow through DgcB and ETF is therefore modeled from the genetically supported, mechanistically proposed Chromohalobacter system. Exact KT2440 accessions and reviewed non-PSEPK exemplars are retained explicitly.

5Nodes
2Parts
1Variant Sets
2Variants
4Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • bacterial_dimethylglycine_sarcosine_catabolism-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (8/17 grounded genes reviewed)

7 complete review(s) · 1 with deep research · 9 missing review · 7 reviewed but lacking deep research

Gene Review Complete Deep research
dgcA Q88R24 ✓ 2/3 ✗
dgcB Q88R23 ✓ ✓ ✗
monomeric sarcosine oxidase (Arthrobacter sp. TE1826) P40873 ✗ — —
PP_0312 Q88R22 ✓ ✓ ✗
PP_0313 Q88R21 ✓ ✓ ✗
EtfB (Chromohalobacter salexigens) Q1QYV8 ✗ — —
EtfA (Chromohalobacter salexigens) Q1QYV9 ✗ — —
Csal_0991 (Chromohalobacter salexigens) Q1QYW0 ✗ — —
DdhC (Chromohalobacter salexigens) Q1QYW1 ✗ — —
SoxG (Corynebacterium sp. U-96) Q50LE9 ✗ — —
SoxA (Corynebacterium sp. U-96) Q50LF0 ✗ — —
SoxD (Corynebacterium sp. U-96) Q50LF1 ✗ — —
SoxB (Corynebacterium sp. U-96) Q50LF2 ✗ — —
soxA Q88R09 ✓ ✓ ✓
soxB Q88R11 ✓ ✓ ✗
soxD Q88R10 ✓ ✓ ✗
soxG Q88R08 ✓ ✓ ✗

Details

Context
bacteriaNCBITaxon:2
Bacterial dimethylglycine and sarcosine catabolismMetabolic Pathwaybacterial_dimethylglycine_sarcosine_catabolism
Context
bacteriaNCBITaxon:2

Connections

Sarcosine formed by dimethylglycine demethylation is the substrate of sarcosine oxidase.
Part 1: dimethylglycine demethylation to sarcosine
Dimethylglycine conversion to sarcosineReactiondimethylglycine_to_sarcosine

Annotons

DgcAB dimethylglycine demethylation
dgcab_complex_activity
Participant: Protein Complex: bacterial two-component dimethylglycine dehydrogenase
Protein Complex:
bacterial two-component dimethylglycine dehydrogenase
Active units:
DgcA flavin subunit
Participant: Family: DgcA flavin oxidoreductase family
Family:
DgcA flavin oxidoreductase family Use exact DgcA representatives in a conserved dgcA-dgcB-etfA-etfB neighborhood. The broad PANTHER oxidoreductase family is not sufficient to assign this role.
Representative Members: DgcA (Pseudomonas putida KT2440)UniProtKB:Q88R24 DdhC (Chromohalobacter salexigens)UniProtKB:Q1QYW1
DgcB membrane iron-sulfur subunit
Participant: Family: DgcB membrane iron-sulfur oxidoreductase family
Family:
DgcB membrane iron-sulfur oxidoreductase family Use exact membrane-anchored DgcB representatives adjacent to DgcA and the pathway ETF. Generic HdrC/FadF-like iron-sulfur family membership is not sufficient.
Representative Members: DgcB (Pseudomonas putida KT2440)UniProtKB:Q88R23 Csal_0991 (Chromohalobacter salexigens)UniProtKB:Q1QYW0

Function

N,N-dimethylglycine dehydrogenase (ferredoxin) activity
Substrates: dimethylglycine oxidized DgcB 2[4Fe-4S] ferredoxin water
Products: sarcosine formaldehyde reduced DgcB 2[4Fe-4S] ferredoxin 2 protons

This is EC 1.5.7.3 / RHEA:74167. DgcB is the immediate iron-sulfur acceptor. GO:0047865 is not used because that GO term specifies direct reduction of ETF rather than ferredoxin.

Pathway-associated electron transfer flavoprotein
dimethylglycine_catabolism_etf_activity
Participant: Protein Complex: dimethylglycine catabolism ETF heterodimer
Protein Complex:
dimethylglycine catabolism ETF heterodimer
Active units:
ETF alpha subunit
Participant: Family: dimethylglycine catabolism ETF alpha-subunit family
Family:
dimethylglycine catabolism ETF alpha-subunit family Pathway assignment requires an exact curated representative in the conserved dgcA-dgcB-etfA-etfB neighborhood; generic ETF alpha/FixB family membership is insufficient.
Representative Members: PP_0312 (Pseudomonas putida KT2440)UniProtKB:Q88R22 EtfA (Chromohalobacter salexigens)UniProtKB:Q1QYV9
ETF beta subunit
Participant: Family: dimethylglycine catabolism ETF beta-subunit family
Family:
dimethylglycine catabolism ETF beta-subunit family Pathway assignment requires an exact curated representative paired with the pathway ETF alpha subunit beside dgcAB; generic ETF beta/FixA family membership is insufficient.
Representative Members: PP_0313 (Pseudomonas putida KT2440)UniProtKB:Q88R21 EtfB (Chromohalobacter salexigens)UniProtKB:Q1QYV8

Function

electron transfer from reduced DgcB toward an unresolved acceptorGO:0009055

The ETF heterodimer is proposed to accept reducing equivalents from reduced DgcB. Direct transfer and the downstream acceptor have not been established for KT2440.

Part 2: sarcosine demethylation to glycine
Sarcosine conversion to glycineReactionsarcosine_to_glycine
Variant set: Sarcosine oxidase architecture by enzyme architecture (One Or More)
Tetrahydrofolate-coupled SoxABDG heterotetramerReactiontetrameric_soxabdg_variant

Annotons

SoxABDG sarcosine oxidase activity
soxabdg_complex_activity
Participant: Protein Complex: tetrameric sarcosine oxidase complex
Protein Complex:
tetrameric sarcosine oxidase complexGO:0032921
Active units:
SoxA alpha subunit
Participant: Family: tetrameric sarcosine oxidase alpha-subunit family
Family:
tetrameric sarcosine oxidase alpha-subunit family
Representative Members: SoxA (Pseudomonas putida KT2440)UniProtKB:Q88R09 SoxA (Corynebacterium sp. U-96)UniProtKB:Q50LF0
SoxB beta subunit
Participant: Family: tetrameric sarcosine oxidase beta-subunit family
Family:
tetrameric sarcosine oxidase beta-subunit family Use exact SoxB representatives encoded with SoxA, SoxD, and SoxG; the broad sarcosine-dehydrogenase- related PANTHER family is not role-specific.
Representative Members: SoxB (Pseudomonas putida KT2440)UniProtKB:Q88R11 SoxB (Corynebacterium sp. U-96)UniProtKB:Q50LF2
SoxD delta subunit
Participant: Family: tetrameric sarcosine oxidase delta-subunit family
Family:
tetrameric sarcosine oxidase delta-subunit family
Representative Members: SoxD (Pseudomonas putida KT2440)UniProtKB:Q88R10 SoxD (Corynebacterium sp. U-96)UniProtKB:Q50LF1
SoxG gamma subunit
Participant: Family: tetrameric sarcosine oxidase gamma-subunit family
Family:
tetrameric sarcosine oxidase gamma-subunit family
Representative Members: SoxG (Pseudomonas putida KT2440)UniProtKB:Q88R08 SoxG (Corynebacterium sp. U-96)UniProtKB:Q50LE9

Function

sarcosine oxidase (5,10-methylenetetrahydrofolate-forming) activity
Substrates: sarcosine tetrahydrofolate oxygen
Products: glycine 5,10-methylenetetrahydrofolate hydrogen peroxide

This is EC 1.5.3.24 / RHEA:70455. No current GO molecular function term accurately represents the folate-coupled reaction; GO:0008115 is reserved for the water/formaldehyde chemistry. In low folate, the same complex can release formaldehyde conditionally.

Monomeric sarcosine oxidaseReactionmonomeric_sarcosine_oxidase_variant

Annotons

Monomeric sarcosine oxidase activity
monomeric_sarcosine_oxidase_activity
Participant: Family: monomeric sarcosine oxidase family
Family:
monomeric sarcosine oxidase family
Representative Members: monomeric sarcosine oxidase (Arthrobacter sp. TE1826)UniProtKB:P40873

Function

sarcosine oxidase activityGO:0008115
Substrates: sarcosine oxygen water
Products: glycine formaldehyde hydrogen peroxide