Phosphorylated L-serine biosynthesis

A reusable three-reaction pathway that converts the glycolytic intermediate 3-phospho-D-glycerate to L-serine through 3-phosphooxypyruvate and O-phospho-L-serine. NAD+-dependent D-3-phosphoglycerate dehydrogenase catalyses the first, committed oxidation; a pyridoxal 5'-phosphate-dependent phosphoserine aminotransferase transfers the amino group of L-glutamate to 3-phosphooxypyruvate; and a Mg2+-dependent HAD-family phosphoserine phosphatase releases free L-serine. The module represents the conserved SerA, SerC and SerB reaction roles independently of genomic arrangement and of which paralog carries them: budding yeast, for example, has two phosphoglycerate dehydrogenase paralogs. L-serine made this way is also the main precursor of glycine and of folate one-carbon units, but those conversions, and the alternative glyoxylate and threonine routes to glycine and serine, are separate modules. Additional activities of individual enzymes, including 2-oxoglutarate reduction to D-2-hydroxyglutarate by some SerA proteins and vitamin B6 precursor transamination by some SerC proteins, are outside this pathway boundary.

MODULE:phosphorylated_serine_biosynthesisDRAFTMetabolic Pathwaymodules/phosphorylated_serine_biosynthesis.yaml
L-serine biosynthetic processGO:0006564
GO:0006564
L-serine biosynthetic process
GO:0006564 provides the biological-process context for synthesis of L-serine.
YeastPathways:SERSYN-PWY
L-serine biosynthesis I (S. cerevisiae, SGD YeastPathways)
The SGD YeastCyc pathway lists the three reactions with SER3 and SER33 (EC 1.1.1.95), SER1 (EC 2.6.1.52) and SER2 (EC 3.1.3.3). All four catalyst assignments are retained and no catalyst is missing.
YeastPathways:PWY3O-261
superpathway of serine and glycine biosynthesis (S. cerevisiae, SGD YeastPathways)
The YeastCyc superpathway repeats the three SERSYN-PWY reactions; its SHMT, threonine aldolase and alanine:glyoxylate aminotransferase reactions are modelled in glycine_serine_interconversion.
PMID:14154
Transient kinetic and deuterium isotope effect studies on the catalytic mechanism of phosphoglycerate dehydrogenase
Characterized phosphoglycerate dehydrogenase is a V-type allosteric enzyme inhibited by serine; this grounds the regulatory context without making feedback control a required pathway part.
Phosphoglycerate dehydrogenase corresponds to a V-type allosteric enzyme.
PMID:12525494
Ser3p (Yer081wp) and Ser33p (Yil074cp) are phosphoglycerate dehydrogenases in Saccharomyces cerevisiae.
SER3 and SER33 are redundant phosphoglycerate dehydrogenases; only the double mutant lacks activity and is a serine/glycine auxotroph on glucose, because the alternative glyoxylate route is glucose-repressed.
Unlike either single mutant, the ser3Delta ser33Delta double mutant lacks detectable phosphoglycerate dehydrogenase activity and is auxotrophic for serine or glycine for growth on glucose media.
PMID:1326413
Genetic analysis of serine biosynthesis and glucose repression in yeast.
ser1 and ser2 mutants in the glycolytic pathway lack phosphoserine transaminase and phosphoserine phosphatase respectively.
The ser1 mutation corresponded to phosphoserine transaminase and ser2 to that of phosphoserine phosphatase.
PMID:8017107
A gene from Saccharomyces cerevisiae which codes for a protein with significant homology to the bacterial 3-phosphoserine aminotransferase.
The yeast SERC (SER1) gene encodes a 3-phosphoserine aminotransferase homolog whose deletion causes serine dependency.
we present the sequence for this yeast SERC, and evidence that its deletion from the yeast genome leads to serine dependency
file:modules/phosphorylated_serine_biosynthesis-deep-research-openscientist.md
OpenScientist research for phosphorylated L-serine biosynthesis
The generic pathway review evaluates the three conserved reaction roles, their chemistry, and lineage-dependent enzyme architectures.
file:PSEPK/serA/serA-ai-review.yaml
PSEPK serA gene review
Q88CM5 supplies the phosphoglycerate dehydrogenase step.
file:PSEPK/serC/serC-ai-review.yaml
PSEPK serC gene review
Q88M07 supplies the phosphoserine aminotransferase step.
file:PSEPK/serB/serB-ai-review.yaml
PSEPK serB gene review
Q88DB8 supplies the phosphoserine phosphatase step.
file:yeast/SER3/SER3-ai-review.yaml
SER3 gene review (S. cerevisiae)
Core function GO:0004617 in L-serine biosynthesis.
file:yeast/SER33/SER33-ai-review.yaml
SER33 gene review (S. cerevisiae)
Core function GO:0004617 in L-serine biosynthesis; main isozyme on glucose.
file:yeast/SER1/SER1-ai-review.yaml
SER1 gene review (S. cerevisiae)
Core function GO:0004648 in L-serine biosynthesis.
file:yeast/SER2/SER2-ai-review.yaml
SER2 gene review (S. cerevisiae)
Core function GO:0036424 in L-serine biosynthesis.
4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • phosphorylated_serine_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

11 gene-function check(s) reflected in core functions · 0 conflict(s) · 3 evidence or coverage gap(s) (16 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
serA_activity PSEPK SerA
UniProtKB:Q88CM5
Family Representative 		phosphoglycerate dehydrogenase activity
GO:0004617 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serA_activity Haemophilus influenzae SerA
UniProtKB:P43885
Family Representative 		phosphoglycerate dehydrogenase activity
GO:0004617 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
serA_activity SER3 (Saccharomyces cerevisiae)
UniProtKB:P40054
Family Representative 		phosphoglycerate dehydrogenase activity
GO:0004617 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serA_activity SER33 (Saccharomyces cerevisiae)
UniProtKB:P40510
Family Representative 		phosphoglycerate dehydrogenase activity
GO:0004617 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serA_activity ser3 (Schizosaccharomyces pombe)
UniProtKB:P87228
Family Representative 		phosphoglycerate dehydrogenase activity
GO:0004617 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity PSEPK SerC
UniProtKB:Q88M07
Family Representative 		O-phospho-L-serine:2-oxoglutarate aminotransferase activity
GO:0004648 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity Escherichia coli SerC
UniProtKB:P23721
Family Representative 		O-phospho-L-serine:2-oxoglutarate aminotransferase activity
GO:0004648 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity SER1 (Saccharomyces cerevisiae)
UniProtKB:P33330
Family Representative 		O-phospho-L-serine:2-oxoglutarate aminotransferase activity
GO:0004648 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity ser1 (Schizosaccharomyces pombe)
UniProtKB:Q10349
Family Representative 		O-phospho-L-serine:2-oxoglutarate aminotransferase activity
GO:0004648 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serB_activity PSEPK SerB
UniProtKB:Q88DB8
Family Representative 		L-phosphoserine phosphatase activity
GO:0036424 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serB_activity Escherichia coli SerB
UniProtKB:P0AGB0
Family Representative 		L-phosphoserine phosphatase activity
GO:0036424 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
serB_activity SER2 (Saccharomyces cerevisiae)
UniProtKB:P42941
Family Representative 		L-phosphoserine phosphatase activity
GO:0036424 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serB_activity ser2 (Schizosaccharomyces pombe)
UniProtKB:O74382
Family Representative 		L-phosphoserine phosphatase activity
GO:0036424 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serA_activity D-3-phosphoglycerate dehydrogenases of the D-isomer-specific 2-hydroxyacid dehydrogenase superfamily
Family 		phosphoglycerate dehydrogenase activity
GO:0004617 		Family Id Missing
The family has no identifier linking it to a curated family review.
serC_activity SerC phosphoserine aminotransferases
PANTHER:PTHR43247:SF1
Family 		O-phospho-L-serine:2-oxoglutarate aminotransferase activity
GO:0004648 		Family Supported
Family review supports GO:0004648 FAMILY_WIDE. Asserted by serine_biosynthesis_one_carbon and phosphorylated_serine_biosynthesis; accepted by every reviewed member, including E. coli and P. putida SerC. The pyridoxal_5_phosphate_biosynthesis module uses SF1 for SerC's separate phosphohydroxythreonine reaction, grounded on the parent transaminase term because GO has no specific term for it.
serB_activity SerB phosphoserine phosphatases
PANTHER:PTHR43344:SF2
Family 		L-phosphoserine phosphatase activity
GO:0036424 		Family Supported
Family review supports GO:0036424 for PANTHER:PTHR43344:SF2. Asserted by serine_biosynthesis_one_carbon and phosphorylated_serine_biosynthesis; accepted by PSPH, SER2, SPBC3H7.07c and P. putida serB.

Gene-review completeness (11/13 grounded genes reviewed)

11 complete review(s) · 5 with deep research · 2 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
Escherichia coli SerB P0AGB0 ✗ — —
Haemophilus influenzae SerA P43885 ✗ — —
SER1 P33330 ✓ ✓ ✓
SER2 P42941 ✓ ✓ ✓
SER3 P40054 ✓ ✓ ✓
SER33 P40510 ✓ ✓ ✓
serA Q88CM5 ✓ ✓ ✗
serB Q88DB8 ✓ ✓ ✗
serC P23721 ✓ ✓ ✗
serC Q88M07 ✓ ✓ ✓
SPAC1F12.07 Q10349 ✓ ✓ ✗
SPBC3H7.07c O74382 ✓ ✓ ✗
SPCC364.07 P87228 ✓ ✓ ✗

Details

Phosphorylated L-serine biosynthesisMetabolic Pathwayphosphorylated_serine_biosynthesis
L-serine biosynthetic processGO:0006564

Exact UniProt exemplars delimit the three reaction roles without restricting the module taxonomically. No cellular location or molecular function is repeated at module level; in both yeasts all three enzymes are cytosolic, but plants run the pathway in plastids, so no compartment is asserted. SerC can also catalyze phosphohydroxythreonine transamination in DXP-dependent vitamin B6 biosynthesis, but that separate reaction is not a fourth part of this module. Some bacterial SerA proteins use an ACT domain for L-serine feedback, but effector sensitivity is a lineage- and sequence-dependent regulatory property rather than an additional pathway part. No ancestral PTN is asserted: the local PAINT exports identify family-level IBD nodes but do not establish that the PSEPK targets descend from those nodes. ALIGN with YeastPathways (2026-10): SERSYN-PWY maps one-to-one onto the three parts and its catalysts (SER3, SER33, SER1, SER2) are all correct; no yeast enzyme is missing. The reverse-written YeastCyc transaminase equation (PSERTRANSAM-RXN) is the same reaction. The step-1 family anchor PTHR43761:SF1 was removed because S. cerevisiae SER3/SER33 are classified in PTHR42789:SF1 while S. pombe ser3 and the bacterial enzymes are in PTHR43761:SF1; the role is defined by GO:0004617 instead. Ser3/Ser33 also reduce 2-oxoglutarate to D-2-hydroxyglutarate (side activity, excluded). The yeast glyoxylate (AGX1 plus SHMT) and threonine aldolase (GLY1) routes to serine and glycine, which make the SER pathway conditionally dispensable on non-fermentable carbon sources, are in glycine_serine_interconversion. GO-CAM comparison: both models agree with the module (MF, process, cytosol); the YeastPathways model has no causal edges, and the PomBase model links ser3 -> ser1 -> ser2 with RO:0002413.

Connections

SerA supplies 3-phosphooxypyruvate to SerC.
SerC supplies O-phospho-L-serine to SerB.
Part 1: 3-phosphooxypyruvate formation
Phosphoglycerate dehydrogenaseReactionphosphoglycerate_dehydrogenase_step

Annotons

Phosphoglycerate dehydrogenase
serA_activity
Participant: Family: D-3-phosphoglycerate dehydrogenases of the D-isomer-specific 2-hydroxyacid dehydrogenase superfamily
Family:
D-3-phosphoglycerate dehydrogenases of the D-isomer-specific 2-hydroxyacid dehydrogenase superfamily No single PANTHER family is asserted. The bacterial and fission-yeast enzymes fall in PTHR43761:SF1, whereas budding yeast SER3 and SER33 are classified in PTHR42789:SF1 (UniProt PANTHER cross-references), so a family id would exclude one set of verified catalysts. The required GO:0004617 function defines the role.
Representative Members: PSEPK SerAUniProtKB:Q88CM5 Haemophilus influenzae SerAUniProtKB:P43885 SER3 (Saccharomyces cerevisiae)UniProtKB:P40054 SER33 (Saccharomyces cerevisiae)UniProtKB:P40510 ser3 (Schizosaccharomyces pombe)UniProtKB:P87228
Required Function:
phosphoglycerate dehydrogenase activityGO:0004617

Function

phosphoglycerate dehydrogenase activityGO:0004617
Substrates: 3-phospho-D-glycerate NAD+
Products: 3-phosphooxypyruvate NADH proton

Oxidizes a glycolytic intermediate to the first committed phosphorylated-serine precursor.

Part 2: O-phospho-L-serine formation
Phosphoserine aminotransferaseReactionphosphoserine_aminotransferase_step

Annotons

Phosphoserine aminotransferase
serC_activity
Participant: Family: SerC phosphoserine aminotransferases
Family:
SerC phosphoserine aminotransferasesPANTHER:PTHR43247:SF1
Representative Members: PSEPK SerCUniProtKB:Q88M07 Escherichia coli SerCUniProtKB:P23721 SER1 (Saccharomyces cerevisiae)UniProtKB:P33330 ser1 (Schizosaccharomyces pombe)UniProtKB:Q10349
Required Function:
O-phospho-L-serine:2-oxoglutarate aminotransferase activityGO:0004648

Function

O-phospho-L-serine:2-oxoglutarate aminotransferase activityGO:0004648
Substrates: 3-phosphooxypyruvate L-glutamate
Products: O-phospho-L-serine 2-oxoglutarate

Transfers an amino group from glutamate to 3-phosphooxypyruvate.

Part 3: L-serine formation
Phosphoserine phosphataseReactionphosphoserine_phosphatase_step

Annotons

Phosphoserine phosphatase
serB_activity
Participant: Family: SerB phosphoserine phosphatases
Family:
SerB phosphoserine phosphatasesPANTHER:PTHR43344:SF2
Representative Members: PSEPK SerBUniProtKB:Q88DB8 Escherichia coli SerBUniProtKB:P0AGB0 SER2 (Saccharomyces cerevisiae)UniProtKB:P42941 ser2 (Schizosaccharomyces pombe)UniProtKB:O74382
Required Function:
L-phosphoserine phosphatase activityGO:0036424

Function

L-phosphoserine phosphatase activityGO:0036424
Substrates: O-phospho-L-serine water
Products: L-serine phosphate

Hydrolyzes O-phospho-L-serine to free L-serine.