Bacterial phosphatidylethanolamine biosynthesis through phosphatidylserine

A reusable two-reaction module for de novo phosphatidylethanolamine biosynthesis from CDP-diacylglycerol in bacteria. Phosphatidylserine synthase (PssA) transfers the phosphatidyl group of CDP-diacylglycerol to L-serine to form phosphatidylserine, and pyruvoyl-dependent phosphatidylserine decarboxylase (Psd) converts phosphatidylserine to phosphatidylethanolamine and CO2 at the cytoplasmic membrane. The first step is carried out by two unrelated enzyme architectures: a type-I, peripheral-membrane PssA of the phospholipase D superfamily, typical of gamma- and some beta-proteobacteria such as Escherichia coli, and a type-II, integral-membrane CDP-alcohol phosphatidyltransferase PssA, typical of Gram-positive bacteria such as Bacillus subtilis. Some genomes, such as Pseudomonas putida KT2440, encode both. The decarboxylation step is performed by a single conserved Psd family whose proenzyme self-cleaves to generate the pyruvoyl prosthetic group.

MODULE:bacterial_phosphatidylethanolamine_biosynthesisCOMPLETECONCRETEMetabolic Pathwaymodules/bacterial_phosphatidylethanolamine_biosynthesis.yaml
phosphatidylethanolamine biosynthetic processGO:0006646
file:modules/bacterial_phosphatidylethanolamine_biosynthesis-deep-research-openscientist.md
OpenScientist review of bacterial phosphatidylethanolamine biosynthesis
The generic module review evaluates the reusable two-reaction boundary, alternative PssA architectures, and Psd-dependent terminal reaction. It was used for leads only; each claim retained here is grounded in the primary literature or curated records cited below.
file:projects/P_PUTIDA/deep-research/PSEPK__bacterial_phosphatidylethanolamine_biosynthesis__ppu00564-deep-research-openscientist.md
OpenScientist review of the module, ppu00564, and PSEPK
The module/pathway/taxon review for the P. putida KT2440 exemplar finds both reactions covered, supports distinct Q88GQ4 and Q88DZ1 PssA architectures, and identifies paralog dominance rather than pathway satisfiability as the open issue.
GO:0006646
phosphatidylethanolamine biosynthetic process
GO:0006646 captures biosynthesis of phosphatidylethanolamine.
RHEA:16913
CDP-diacylglycerol-serine O-phosphatidyltransferase reaction
Rhea 16913 defines formation of phosphatidylserine from CDP-diacylglycerol and L-serine.
RHEA:20828
phosphatidylserine decarboxylase reaction
Rhea 20828 defines decarboxylation of phosphatidylserine to phosphatidylethanolamine.
PMID:39693441
Structural basis for membrane association and catalysis by phosphatidylserine synthase in Escherichia coli
The E. coli PssA structure study defines PLD-superfamily peripheral-membrane PssA as type I and integral-membrane CDP-alcohol phosphatidyltransferase PssA as type II, and shows that membrane-bound type-I PssA is the active form.
PMID:179992
Phosphatidylserine synthetase mutants of Escherichia coli. Genetic mapping and membrane phospholipid composition.
E. coli pss mutants lose phosphatidylethanolamine (66% to 32% of lipid phosphorus) while phosphatidylglycerol and cardiolipin rise, placing PssA on the PE branch.
PMID:1093166
Biogenesis of membrane lipids: mutants of Escherichia coli with temperature-sensitive phosphatidylserine decarboxylase.
Thermolabile psd mutants accumulate phosphatidylserine, showing Psd performs the last step leading to phosphatidylethanolamine.
PMID:8002567
Cloning, sequencing, and expression in Escherichia coli of the Bacillus subtilis gene for phosphatidylserine synthase.
The hydrophobic, membrane-bound B. subtilis PS synthase complements an E. coli pssA mutant, showing that the two unrelated architectures fill the same pathway step.
PMID:9422599
Cloning, sequencing, and disruption of the Bacillus subtilis psd gene coding for phosphatidylserine decarboxylase.
B. subtilis psd lies just downstream of pss; the psd null mutant has no phosphatidylethanolamine and accumulates phosphatidylserine.
PMID:21895997
The glycerophospholipid inventory of Pseudomonas putida is conserved between strains and enables growth condition-related alterations
KT2440 lipidomics detects phosphatidylethanolamine as the major membrane phospholipid and reconstructs both pssA and pssA-2 candidates upstream of psd.

The module begins with CDP-diacylglycerol and L-serine and ends with phosphatidylethanolamine. CDP-diacylglycerol synthesis, phosphatidylglycerol and cardiolipin branches (bacterial_phosphatidylglycerol_cardiolipin_biosynthesis), lipid acyl-chain remodeling, and alternative phosphatidylethanolamine routes such as the Kennedy pathway are outside the boundary. The eukaryotic CHO1/PSD1/PSD2 implementation of the same two reactions is modeled in cdp_dag_phospholipid_synthesis, because its PS synthase steps are ER-localized and its decarboxylases mitochondrial or endomembrane; this module is therefore kept bacterial rather than generalized to all organisms. Psd autocatalytic maturation is required for activity but is a property of the terminal enzyme rather than a separate pathway reaction. Bacterial phosphatidylserine synthases occur in mechanistically distinct type-I and type-II architectures; these type names follow the PssA nomenclature of PMID:39693441. UniProt's CDP-alcohol phosphatidyltransferase class-I/class-II family labels describe a different classification axis and appear inverted relative to the PssA type names. PANTHER family groundings: type-I PssA sits in PTHR12586:SF1, the only subfamily of PTHR12586, whose official name refers to mitochondrial PGS1 because the subfamily also contains eukaryotic PGP synthases; the PAINT node PTN001758495 restricts the annoton to the phosphatidylserine-synthase clade. Type-II PssA sits in PTHR14269:SF61 (P. putida PP_4677, also yeast CHO1) and PTHR14269:SF59 (B. subtilis PssA). Bacterial Psd sits mainly in PTHR10067:SF6 (with eukaryotic PSD1) and partly in SF17. The PTHR12586, PTHR14269 and PTHR10067 family reviews adjudicate these scopes.

5Nodes
2Parts
1Variant Sets
2Variants
3Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • bacterial_phosphatidylethanolamine_biosynthesis-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.

Function consistency and core coverage

7 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
type_i_pssa_activity PssA (Escherichia coli K-12)
UniProtKB:P23830
Family Representative
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
type_i_pssa_activity PssA (Pseudomonas putida KT2440)
UniProtKB:Q88GQ4
Family Representative
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
type_ii_pssa_activity PssA (Bacillus subtilis 168)
UniProtKB:P39823
Family Representative
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
type_ii_pssa_activity PP_4677 (Pseudomonas putida KT2440)
UniProtKB:Q88DZ1
Family Representative
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
psd_activity Psd (Escherichia coli K-12)
UniProtKB:P0A8K1
Family Representative
phosphatidylserine decarboxylase activity
GO:0004609
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
psd_activity Psd (Pseudomonas putida KT2440)
UniProtKB:Q88DB9
Family Representative
phosphatidylserine decarboxylase activity
GO:0004609
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
psd_activity Psd (Bacillus subtilis 168)
UniProtKB:P39822
Family Representative
phosphatidylserine decarboxylase activity
GO:0004609
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
type_i_pssa_activity type-I (PLD-superfamily) phosphatidylserine synthase
PANTHER:PTHR12586:SF1
Family
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Family Supported
Family review supports GO:0003882 for PANTHER:PTHR12586:SF1. Applies only to the type-I PssA clade (PTN001758495) inside SF1. Must not descend to eukaryotic PGS1, even though the family is named after the PS-synthase reaction. Yeast PGS1 was originally proposed to be a second PS synthase and was then shown to be the PGP synthase.
type_ii_pssa_activity type-II (integral-membrane CDP-alcohol phosphatidyltransferase) phosphatidylserine synthase
PANTHER:PTHR14269:SF61
Family
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Family Supported
Family review supports GO:0003882 for PANTHER:PTHR14269:SF61. Type-II PS synthases only: SF61 (CHO1, pps1, PP_4677, mycobacterial and Helicobacter PssA) and SF59 (B. subtilis PssA). No PAINT node in this family asserts it, so yeast CHO1 and S. pombe pps1 receive no PS-synthase IBA. That is a curation gap. The archaeal Methanocaldococcus member of SF61 (Q58609) was not assessed for its acceptor specificity.
type_ii_pssa_activity type-II (integral-membrane CDP-alcohol phosphatidyltransferase) phosphatidylserine synthase
PANTHER:PTHR14269:SF59
Family
CDP-diacylglycerol-serine O-phosphatidyltransferase activity
GO:0003882
Family Supported
Family review supports GO:0003882 for PANTHER:PTHR14269:SF59. Type-II PS synthases only: SF61 (CHO1, pps1, PP_4677, mycobacterial and Helicobacter PssA) and SF59 (B. subtilis PssA). No PAINT node in this family asserts it, so yeast CHO1 and S. pombe pps1 receive no PS-synthase IBA. That is a curation gap. The archaeal Methanocaldococcus member of SF61 (Q58609) was not assessed for its acceptor specificity.
psd_activity pyruvoyl-dependent phosphatidylserine decarboxylase
PANTHER:PTHR10067:SF6
Family
phosphatidylserine decarboxylase activity
GO:0004609
Family Supported
Family review supports GO:0004609 for PANTHER:PTHR10067:SF6. Safe for the PS decarboxylase subfamilies checked here: SF6 (type I, bacterial and mitochondrial), SF17 (PSD2-type) and SF19 (S. pombe psd2). Not safe family-wide, because SF9 psiD/iboD are tryptophan decarboxylases. Subfamilies without Swiss-Prot evidence (SF7, SF11, SF13, SF16, SF18, SF20, SF21) were not examined, although several carry PSD names.
psd_activity pyruvoyl-dependent phosphatidylserine decarboxylase
PANTHER:PTHR10067:SF17
Family
phosphatidylserine decarboxylase activity
GO:0004609
Family Supported
Family review supports GO:0004609 for PANTHER:PTHR10067:SF17. Safe for the PS decarboxylase subfamilies checked here: SF6 (type I, bacterial and mitochondrial), SF17 (PSD2-type) and SF19 (S. pombe psd2). Not safe family-wide, because SF9 psiD/iboD are tryptophan decarboxylases. Subfamilies without Swiss-Prot evidence (SF7, SF11, SF13, SF16, SF18, SF20, SF21) were not examined, although several carry PSD names.

Gene-review completeness (7/7 grounded genes reviewed)

7 complete review(s) · 3 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
PP_4677 Q88DZ1 ✓ ✓ ✓
psd P0A8K1 ✓ ✓ ✗
psd P39822 ✓ ✓ ✗
psd Q88DB9 ✓ ✓ ✓
pssA P23830 ✓ ✓ ✗
pssA P39823 ✓ ✓ ✗
pssA Q88GQ4 ✓ ✓ ✓

Details

Context
bacteriaNCBITaxon:2
Bacterial phosphatidylethanolamine biosynthesisMetabolic Pathwaybacterial_phosphatidylethanolamine_biosynthesis
phosphatidylethanolamine biosynthetic processGO:0006646
Context
bacteriaNCBITaxon:2

Connections

PssA supplies phosphatidylserine to Psd.
Part 1: phosphatidylserine formation
PssA-dependent phosphatidylserine formationReactionpssa_phosphatidylserine_formation
Variant set: Bacterial phosphatidylserine synthase architecture by enzyme architecture (One Or More)
Type-I peripheral-membrane PssAReactiontype_i_pssa

Annotons

Type-I PssA phosphatidylserine synthase activity
type_i_pssa_activity
Participant: Family: type-I (PLD-superfamily) phosphatidylserine synthase
Family:
type-I (PLD-superfamily) phosphatidylserine synthasePANTHER:PTHR12586:SF1 PTHR12586:SF1, the family's only subfamily, holds both bacterial type-I PssA and eukaryotic PGS1 despite its name; the ancestral node PTN001758495 restricts this annoton to the phosphatidylserine-synthase clade.
Representative Members: PssA (Escherichia coli K-12)UniProtKB:P23830 PssA (Pseudomonas putida KT2440)UniProtKB:Q88GQ4

Function

CDP-diacylglycerol-serine O-phosphatidyltransferase activityGO:0003882
Substrates: CDP-diacylglycerol L-serine
Products: phosphatidylserine CMP proton

Processes

phosphatidylethanolamine biosynthetic processGO:0006646

Locations

plasma membraneGO:0005886

Supplies phosphatidylserine to Psd.

Type-II integral-membrane PssAReactiontype_ii_pssa

Annotons

Type-II PssA phosphatidylserine synthase activity
type_ii_pssa_activity
Participant: Family: type-II (integral-membrane CDP-alcohol phosphatidyltransferase) phosphatidylserine synthase
Family:
type-II (integral-membrane CDP-alcohol phosphatidyltransferase) phosphatidylserine synthase The two exemplars sit in different PTHR14269 phosphatidylserine-synthase subfamilies, so both are listed; both also carry InterPro IPR004533 (CDP-diacylglycerol--serine O-phosphatidyltransferase) and NCBIfam TIGR00473.
Representative Members: PssA (Bacillus subtilis 168)UniProtKB:P39823 PP_4677 (Pseudomonas putida KT2440)UniProtKB:Q88DZ1

Function

CDP-diacylglycerol-serine O-phosphatidyltransferase activityGO:0003882
Substrates: CDP-diacylglycerol L-serine
Products: phosphatidylserine CMP proton

Processes

phosphatidylethanolamine biosynthetic processGO:0006646

Locations

plasma membraneGO:0005886

Supplies phosphatidylserine to Psd.

Part 2: phosphatidylethanolamine formation
Psd-dependent phosphatidylethanolamine formationReactionpsd_phosphatidylethanolamine_formation

Annotons

Psd phosphatidylserine decarboxylase activity
psd_activity
Participant: Family: pyruvoyl-dependent phosphatidylserine decarboxylase
Family:
pyruvoyl-dependent phosphatidylserine decarboxylase Bacterial Psd falls mainly in PTHR10067:SF6, which it shares with eukaryotic mitochondrial PSD1 despite the subfamily name, and partly in SF17; the base family is not used because its SF9 members are tryptophan decarboxylases.
Representative Members: Psd (Escherichia coli K-12)UniProtKB:P0A8K1 Psd (Pseudomonas putida KT2440)UniProtKB:Q88DB9 Psd (Bacillus subtilis 168)UniProtKB:P39822

Function

phosphatidylserine decarboxylase activityGO:0004609
Substrates: phosphatidylserine proton
Products: phosphatidylethanolamine carbon dioxide

Processes

phosphatidylethanolamine biosynthetic processGO:0006646

Locations

plasma membraneGO:0005886

Completes phosphatidylethanolamine biosynthesis.