Bacterial heptaprenylglyceryl ether-lipid (Ac-HepG) pathway

The heptaprenylglyceryl ether-lipid pathway characterized in Bacillus subtilis, with homologous PcrB chemistry demonstrated in other Caryophanales. It produces heptaprenylglycerol and its acetylated form (Ac-HepG). sn-Glycerol 1-phosphate (G1P) is condensed with all-trans-heptaprenyl diphosphate by the group I GGGPS-family enzyme PcrB to form an ether bond, giving 3-heptaprenyl-sn-glycero-1-phosphate (HepGP); HepGP is dephosphorylated by a phosphatase that has not been assigned to a gene, and the resulting heptaprenylglycerol (HepG) is O-acetylated from acetyl-CoA by YvoF. The product Ac-HepG is not elaborated into a bulk membrane lipid as in Archaea: it is a low-abundance lipophilic acetyl carrier that delivers acetyl groups to the extracytoplasmic face of the membrane, where LhaT (formerly YpjA) transfers them to the alpha-amino group of the N-terminal cysteine of mature diacylglyceryl lipoproteins. The module is of interest because a bacterium here uses three features of archaeal membrane chemistry at once - a G1P backbone, an ether linkage and an isoprenoid chain - to build a carrier cofactor rather than a membrane. Lipoprotein diacylglyceryl transfer and signal-peptide cleavage, which produce LhaT's acceptor, are modelled separately in bacterial_lipoprotein_maturation; isoprenoid (HepPP) supply and the downstream TLR2 immunology are outside the boundary.

MODULE:bacterial_heptaprenylglyceryl_ether_lipidCOMPLETECONCRETEMetabolic Pathwaymodules/bacterial_heptaprenylglyceryl_ether_lipid.yaml
ether lipid biosynthetic processGO:0008611
PMID:34046426
Mini Review: Bacterial Membrane Composition and Its Modulation in Response to Stress.
The 2021 review places HepST/HepPP supply upstream of several branches, and summarizes PcrB, an unassigned phosphatase and YvoF. Its unknown-function wording predates the 2025 lipoprotein-carrier finding; it does not refute that finding.
Finally, heptaprenyl-PP can be coupled to glycerol-1-phosphate by PcrB, and then further processed by an unidentified phosphatase and the YvoF acetyltranferase to generate an ether linked lipid of unknown function
PMID:35976526
The catalytic and structural basis of archaeal glycerophospholipid biosynthesis.
The structural review separates C35 PcrB group Ib from C20 GGGPS chemistry. Shared fold or G1P recognition alone cannot establish HepGP synthesis.
Members of the PcrB sub-family catalyze the transfer of heptaprenyl diphosphate moieties (C35) to G1P forming heptaprenylglycerol phosphate in contrast to the shorter tetraprenyl moieties (C20) transferred by GGGPS
PMID:40626731
Lipoprotein N-terminal modification in Bacillus: a new paradigm for extracellular acetylation and species-dependent Toll-like receptor 2 immunomodulation.
The reconstitution supplied a C20 surrogate donor, so evidence for the native C35 pathway also depends on genetics and earlier native lipid chemistry.
We substituted the commercially available geranylgeranyl pyrophosphate (GGPP) (four isoprenyl repeats) for the native heptaprenyl pyrophosphate (seven isoprenyl repeats) carrier, as both PcrB and YvoF can accept the shorter substrate albeit with less efficiency (30).
PMID:21761520
Functional assignment of an enzyme that catalyzes the synthesis of an archaea-type ether lipid in bacteria.
PcrB is the Bacillales heptaprenylglyceryl phosphate synthase, and its product is dephosphorylated and acetylated in vivo; this establishes the ether-bond-forming step and the existence of the two processing steps.
PcrB, the bacterial homologue of the archaea-specific geranylgeranylglyceryl phosphate synthase, produces heptaprenylglyceryl phosphate in bacillales. The product becomes dephosphorylated and acetylated in vivo.
PMID:27226549
Identification and Characterization of Heptaprenylglyceryl Phosphate Processing Enzymes in Bacillus subtilis.
Defines the module boundary downstream of PcrB: in Bacillales HepGP is dephosphorylated and acetylated rather than receiving a second polyprenyl chain as in archaeal di-ether lipids.
In Bacillales, heptaprenylglyceryl phosphate does not become linked to a second polyprenyl moiety like ether lipids in Archaea but is dephosphorylated and acetylated.
PMID:27226549
Identification and Characterization of Heptaprenylglyceryl Phosphate Processing Enzymes in Bacillus subtilis.
The dephosphorylation step was enriched as an activity but never assigned to a gene product, which is why this module models it with an abstract ANY_WITH_FUNCTION participant.
We enriched the phosphatase activity from a B. subtilis cell extract and suppose that dephosphorylation is catalyzed by the phosphatase PhoB or by any other phosphatase in an unspecific manner.
PMID:40626731
Lipoprotein N-terminal modification in Bacillus: a new paradigm for extracellular acetylation and species-dependent Toll-like receptor 2 immunomodulation.
Gives the four-step chain used as the module's parts, with the dephosphorylation step still unassigned to a gene.
PcrB condenses sn-glycerol 1-phosphate (G1P) with heptaprenyl pyrophosphate (HepPP) to form heptaprenylglyceryl phosphate (28, 29), which is subsequently dephosphorylated by a non-specific phosphatase prior to acetylation by YvoF to form acetylated heptaprenylglyceryl (Ac-HepG) with acetyl-coenzyme A (Ac-CoA) as donor (27).
PMID:40626731
Lipoprotein N-terminal modification in Bacillus: a new paradigm for extracellular acetylation and species-dependent Toll-like receptor 2 immunomodulation.
The sequence from prenyl transfer through lipoprotein acetylation was reconstituted using PcrB, calf intestinal alkaline phosphatase, YvoF and LhaT-containing E. coli membranes. The assay supplied G1P and substituted a C20 geranylgeranyl donor for the native C35 donor; it neither tests EgsA supply nor establishes native C35 flux or membrane crossing.
While the entire pathway could be reconstituted in vitro with just PcrB, YvoF, a non-specific phosphatase, and LhaT (YpjA) (Fig. 3), it is presently unclear how Ac-HepG/HepG transverses the membrane
PMID:40626731
Lipoprotein N-terminal modification in Bacillus: a new paradigm for extracellular acetylation and species-dependent Toll-like receptor 2 immunomodulation.
Genetic requirement in vivo: loss of pcrB, yvoF or ypjA (lhaT) abolishes lipoprotein N-acetylation, which is what licenses treating the carrier pathway and its consumer as one functional unit.
Only pcrB, yvoF, and ypjA fully suppressed TLR2 activity, indicating these genes are strictly required for Ac-LP synthesis.
PMID:40626731
Lipoprotein N-terminal modification in Bacillus: a new paradigm for extracellular acetylation and species-dependent Toll-like receptor 2 immunomodulation.
The pathway's product is a catalytic acetyl carrier, not a structural membrane lipid; this is the reason the module is typed as a metabolic pathway for a cofactor rather than as membrane-lipid biosynthesis.
A catalytic role as a transient carrier for acetyl groups, as opposed to being a structural membrane building block for an archeal-type lipid with ether-linked isoprenoid chains, is more consistent with the low overall abundance of HepG/Ac-HepG observed in B. subtilis membranes (28).
PMID:24684232
A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization.
Family scoping for the ether-bond step: only group I bacterial members of the GGGPS family are heptaprenylglyceryl phosphate synthases, so the module's family grounding is the HepGP synthase subfamily, not GGGPS as a whole.
the previously uncharacterized bacterial enzymes from group II have GGGPS activity like the archaeal enzymes and differ from the bacterial group I enzymes that are heptaprenylglyceryl phosphate synthases
file:modules/bacterial_lipoprotein_maturation.yaml
Bacterial lipoprotein maturation module
Adjacent module, not duplicated here. It models Lgt diacylglyceryl transfer and LspA signal-peptide cleavage, which generate the diacylglyceryl lipoprotein (DA-LP) that LhaT acetylates, and it already records that the terminal modification of the mature lipoprotein is lineage-variable rather than always Lnt-type N-acylation.
file:genes/BACSU/pcrB/pcrB-notes.md
BACSU pcrB curation notes
Worked evidence for the PcrB step, including the strict G1P acceptor specificity, the Mg2+ requirement, the decision to keep GO:0046474 and add GO:0008611 beside it rather than choose between them (GO:0008611 is not a descendant of GO:0046474, so replacing would discard a true claim), and the carrier (not membrane-lipid) reading of the pathway's purpose.
file:genes/BACSU/egsA/egsA-notes.md
BACSU egsA curation notes
Worked evidence for the G1P-supply step, including purified AraM/EgsA activity and the unresolved assignment of native G1P supply to PcrB. Kinetic substrate preferences do not establish physiological direction or pathway flux.

See bacterial_heptaprenylglyceryl_ether_lipid-notes.md for the boundary argument, the GO term gaps found (no term for archaeal-type isoprenoid-ether lipid biosynthesis, for a prenyl-lipid acetyl-carrier cycle, or for heptaprenylglyceryl phosphate phosphatase activity), the reasons the PcrB and EgsA PANTHER/PAINT ancestral nodes were left unasserted, and the expected QC notices. Comparative reviews distinguish the BACSU carrier pathway from GEOKA and STAA1 PcrB step evidence and the FLAJ1 C20-GGGPS comparator. Carrier-pathway activity in another species requires evidence beyond a family match; native G1P supply and the phosphatase remain unassigned.

7Nodes
5Parts
1Variant Sets
1Variants
5Annotons
4Connections

Derived QC

Recommended-field compliance

42.9% recommended fields populated
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Module deep research

✗ none found

No MODULE:bacterial_heptaprenylglyceryl_ether_lipid deep-research report alongside the module YAML.

Leaf nodes lacking representative members

1 leaf node(s) with no concrete protein grounding:

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • ether_bond_formation → hepgp_dephosphorylation [NOT_CHECKED]
    Continuity is on HepGP (CHEBI:64781), not a CoA thioester, so the automated CoA-carrier check cannot see it. The identity of the intermediate is established; only the enzyme of the downstream step is unassigned.
  • hepgp_dephosphorylation → hepg_acetylation [NOT_CHECKED]
    Continuity is on heptaprenylglycerol, which has no ChEBI identifier, so it cannot be checked automatically; it is supported by the stepwise in vitro reconstitution.

Function consistency and core coverage

6 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (11 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
g1p_dehydrogenase egsA/araM (Bacillus subtilis exemplar)
UniProtKB:P94527
Family Representative 		glycerol-1-phosphate dehydrogenase [NAD(P)+] activity
GO:0050492 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hepgp_synthase pcrB (Bacillus subtilis exemplar)
UniProtKB:O34790
Family Representative 		heptaprenylglyceryl phosphate synthase activity
GO:0120536 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hepgp_synthase pcrB (Geobacillus kaustophilus HTA426)
UniProtKB:Q5L3C1
Family Representative 		heptaprenylglyceryl phosphate synthase activity
GO:0120536 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hepgp_synthase pcrB (Staphylococcus aureus Mu3)
UniProtKB:A7X435
Family Representative 		heptaprenylglyceryl phosphate synthase activity
GO:0120536 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hepgp_phosphatase ANY_WITH_FUNCTION
Gene 		phosphatase activity (on heptaprenylglyceryl phosphate)
GO:0016791 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
hepg_acetyltransferase yvoF (Bacillus subtilis exemplar)
UniProtKB:O34993
Family Representative 		heptaprenylglycerol O-acetyltransferase activity (acetyl-CoA-dependent)
GO:0016413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
lipoprotein_n_acetyltransferase lhaT/ypjA (Bacillus subtilis exemplar)
UniProtKB:P54392
Family Representative 		lipoprotein N-terminal N-acetyltransferase activity, using acetylated heptaprenylglycerol as donor
GO:0008080 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
g1p_dehydrogenase bacterial glycerol-1-phosphate dehydrogenase (G1PDH, EgsA/AraM) family
PANTHER:PTHR43622:SF1
Family 		glycerol-1-phosphate dehydrogenase [NAD(P)+] activity
GO:0050492 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0050492.
hepgp_synthase bacterial group I GGGPS-family heptaprenylglyceryl phosphate synthase (PcrB) subfamily
PANTHER:PTHR40029:SF2
Family 		heptaprenylglyceryl phosphate synthase activity
GO:0120536 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR40029:SF2.
hepg_acetyltransferase YvoF-related hexapeptide-repeat acetyltransferase subfamily
PANTHER:PTHR43300:SF6
Family 		heptaprenylglycerol O-acetyltransferase activity (acetyl-CoA-dependent)
GO:0016413 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43300:SF6.
lipoprotein_n_acetyltransferase lipoprotein heptaprenylglyceryl N-acetyltransferase (LhaT/YpjA, DUF1405) family
PANTHER:PTHR40042:SF1
Family 		lipoprotein N-terminal N-acetyltransferase activity, using acetylated heptaprenylglycerol as donor
GO:0008080 		Family Function Unreviewed
Family review leaves GO:0008080 UNRESOLVED. P54392/ypjA in B.subtilis168 has directly demonstrated donor-agnostic N-acetyltransferase activity, retained in its gene review. Family-wide or SF1-wide transfer is not established: the primary reports an inactive B.anthracis homolog and sequence context alone is not a sufficient function test. The schema has no positive single-member scope, so this broader scope remains unresolved rather than converting a known member activity into a universal assertion. The assay used recombinant target in membrane preparations, a C20 carrier analogue and mixed acetyl donors; it does not establish purified-LhaT kinetics or native C35 preference.

Gene-review completeness (6/6 grounded genes reviewed)

5 complete review(s) · 0 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
egsA P94527 ✓ 4/5 ✗
pcrB A7X435 ✓ ✓ ✗
pcrB O34790 ✓ ✓ ✗
pcrB Q5L3C1 ✓ ✓ ✗
ypjA P54392 ✓ ✓ ✗
yvoF O34993 ✓ ✓ ✗

Details

Context
BacillalesNCBITaxon:1385
cytoplasmGO:0005737
low-abundance carrier lipid pool
Bacterial heptaprenylglyceryl ether-lipid (Ac-HepG) pathwayMetabolic Pathwaybacterial_heptaprenylglyceryl_ether_lipid

Required G1P supply followed by three carrier-synthesis steps from G1P and heptaprenyl diphosphate to Ac-HepG, plus the optional terminal step in which the carried acetyl group is handed to a lipoprotein. The first four steps run on the cytoplasmic side; the last is catalysed by an integral membrane enzyme acting on an extracytoplasmic acceptor.

ether lipid biosynthetic processGO:0008611
Context
BacillalesNCBITaxon:1385
cytoplasmGO:0005737
low-abundance carrier lipid pool

Connections

g1p_supply -> ether_bond_formation Provides Input For
Supplies the sn-glycerol 1-phosphate acceptor for ether-bond formation.
HepGP is the substrate of the dephosphorylation step.
HepG produced by dephosphorylation is the acetyl acceptor for YvoF; the order was established in vitro, where acetylation follows phosphatase treatment.
Ac-HepG made by YvoF is the acetyl donor used by LhaT; the transfer regenerates HepG for reloading, closing a carrier cycle.
Part 1: sn-glycerol 1-phosphate supply
sn-Glycerol 1-phosphate supplyReactiong1p_supply

Provision of the G1P acceptor. PcrB accepts G1P and not G3P, so a source of the archaeal-type glycerophosphate enantiomer is required. The only characterized bacterial route is NAD(P)H-dependent reduction of glycerone phosphate (DHAP) by a glycerol-1-phosphate dehydrogenase (EgsA/AraM). Whether that enzyme is in fact the in vivo source of the G1P used by PcrB has not been shown, so the step is modelled as a required activity with one known realizer rather than as a proven EgsA-to-PcrB flux.

Variant set: Enzymes that can supply sn-glycerol 1-phosphate by G1P-supplying enzyme [Realizer] (One Or More)
PMID:42286214
Bacterial lipid synthesizing enzymes PlsY and PlsC utilize both stereo-forms of glycerol-phosphate.
This paper cites earlier engineered E. coli lipid production without AraM and infers an unidentified G1P-supply mechanism. It does not identify that mechanism, discover a second enzyme, or prove its use by native B. subtilis PcrB.
other mechanism(s) of G1P biosynthesis must exist in E. coli and possibly other bacteria, as archaeal lipids with the correct chiral structure could be produced even in the absence of AraM

Declared as a REALIZER set with a single modelled carrier on purpose: engineered E. coli produced correctly configured G1P-backbone archaeal lipids without AraM, so at least one further route to G1P exists and is not identifiable. A gap at this step should therefore be read as "activity required, carrier not identified", not as "no route exists".

G1P dehydrogenase (EgsA/AraM) routeReactiong1pdh_route

Annotons

G1P dehydrogenase family: DHAP reduction to sn-glycerol 1-phosphate
g1p_dehydrogenase
Participant: Family: bacterial glycerol-1-phosphate dehydrogenase (G1PDH, EgsA/AraM) family
Family:
bacterial glycerol-1-phosphate dehydrogenase (G1PDH, EgsA/AraM) familyPANTHER:PTHR43622:SF1 PANTHER places EgsA in a heterogeneous subfamily that also contains dehydroquinate and other sugar-phosphate enzymes; the official name is retained verbatim in `term.label` and the intended grouping is given in `preferred_term`. The curated family statement for the exemplar is UniProt's "glycerol-1-phosphate dehydrogenase family" (HAMAP-Rule MF_00497_B, InterPro IPR023003).
Representative Members: egsA/araM (Bacillus subtilis exemplar)UniProtKB:P94527
Required Function:
glycerol-1-phosphate dehydrogenase activityGO:0050492 Required biochemical qualification: PTHR43622:SF1 also contains dehydroquinate and other sugar-phosphate enzymes. Membership alone does not establish G1PDH.

Function

glycerol-1-phosphate dehydrogenase [NAD(P)+] activityGO:0050492 Purified AraM reduces DHAP using NADH and also accepts NADPH less efficiently. The reaction is drawn in the G1P-supplying direction needed by PcrB; this is a biochemical capability, not measured native flux. Cofactor-specific children are GO:0106357 (NAD+) and GO:0106358 (NADP+); native cofactor use is unresolved.
Substrates: glycerone phosphate (dihydroxyacetone phosphate)CHEBI:57642 NADHCHEBI:57945
Products: sn-glycerol 1-phosphateCHEBI:57685 NAD(+)CHEBI:57540
Cofactors: nickel(2+)CHEBI:49786

Processes

ether lipid biosynthetic processGO:0008611

Locations

cytoplasmGO:0005737

Supplies the archaeal-type glycerophosphate enantiomer that the ether-bond-forming step requires. Only known bacterial enzyme for the reaction; not demonstrated to be the in vivo source for PcrB.

Part 2: Ether-bond formation between G1P and the isoprenoid chain
Heptaprenylglyceryl phosphate synthesis (PcrB)Reactionether_bond_formation

PcrB, a homodimeric Mg2+-dependent group I GGGPS-family prenyltransferase, transfers the C35 heptaprenyl moiety of all-trans-heptaprenyl diphosphate to the C3 hydroxyl of sn-glycerol 1-phosphate, forming the ether bond and releasing diphosphate. This is the committed and name-giving step of the module.

Annotons

HepGP synthase subfamily: G1P heptaprenyltransferase
hepgp_synthase
Participant: Family: bacterial group I GGGPS-family heptaprenylglyceryl phosphate synthase (PcrB) subfamily
Family:
bacterial group I GGGPS-family heptaprenylglyceryl phosphate synthase (PcrB) subfamilyPANTHER:PTHR40029:SF2 Group I bacterial members of the GGGPS family are HepGP synthases; group II bacterial members are GGGP synthases, so the subfamily rather than the family is the correct grounding for this activity. UniProt grounds the exemplar further with HAMAP-Rule MF_00112 and Pfam PF01884 (PcrB).
Representative Members: pcrB (Bacillus subtilis exemplar)UniProtKB:O34790 pcrB (Geobacillus kaustophilus HTA426)UniProtKB:Q5L3C1 pcrB (Staphylococcus aureus Mu3)UniProtKB:A7X435

Function

heptaprenylglyceryl phosphate synthase activityGO:0120536
Substrates: sn-glycerol 1-phosphateCHEBI:57685 all-trans-heptaprenyl diphosphateCHEBI:58206
Products: 3-heptaprenyl-sn-glycero-1-phosphate (HepGP)CHEBI:64781 diphosphateCHEBI:33019
Cofactors: magnesium(2+)CHEBI:18420

Processes

ether lipid biosynthetic processGO:0008611

Locations

cytoplasmGO:0005737

Committed step of the module; creates the archaeal-type isoprenoid-ether linkage on a G1P backbone.

Part 3: Dephosphorylation of heptaprenylglyceryl phosphate
HepGP dephosphorylation to heptaprenylglycerol (unassigned phosphatase)Reactionhepgp_dephosphorylation

Hydrolysis of the phosphomonoester of HepGP to give the neutral ether lipid heptaprenylglycerol (HepG). The activity was enriched from a B. subtilis cell extract but never assigned to a gene product; PhoB was suspected and not demonstrated, and the authors explicitly allow that any phosphatase may do it unspecifically. The in vitro reconstitution of the whole pathway used calf intestinal alkaline phosphatase in this position. The step is therefore modelled as a required activity with no participant protein; no gene product is asserted.

Annotons

Unassigned phosphatase acting on heptaprenylglyceryl phosphate
hepgp_phosphatase
Participant: Any With Function: phosphatase activity able to hydrolyse the phosphomonoester of heptaprenylglyceryl phosphate
Required Function:
phosphatase activity able to hydrolyse the phosphomonoester of heptaprenylglyceryl phosphateGO:0016791 Deliberately broad. The responsible B. subtilis enzyme is unknown, the candidate named in the literature (PhoB) was not confirmed, and the activity may be contributed non-specifically by more than one phosphatase. No substrate-specific GO term (heptaprenylglyceryl phosphate phosphatase activity) exists.
Any B. subtilis phosphatase that can dephosphorylate HepGP. This is an activity requirement, not a gene assignment: the module deliberately leaves the participant unidentified rather than naming PhoB, which the source only suspected.
PMID:27226549
Identification and Characterization of Heptaprenylglyceryl Phosphate Processing Enzymes in Bacillus subtilis.
The authors enriched the activity but did not assign it; the named candidate is explicitly a supposition.
We enriched the phosphatase activity from a B. subtilis cell extract and suppose that dephosphorylation is catalyzed by the phosphatase PhoB or by any other phosphatase in an unspecific manner.

Function

phosphatase activity (on heptaprenylglyceryl phosphate)GO:0016791
Substrates: 3-heptaprenyl-sn-glycero-1-phosphate (HepGP)CHEBI:64781
Products: heptaprenylglycerol (HepG) phosphateCHEBI:43474

Processes

ether lipid biosynthetic processGO:0008611

Locations

cytoplasmGO:0005737

Converts the charged intermediate into the neutral ether lipid that YvoF acetylates. Required for the pathway; carried out by an enzyme that has not been identified.

Part 4: Acetylation of heptaprenylglycerol
Heptaprenylglycerol O-acetylation (YvoF)Reactionhepg_acetylation

YvoF transfers an acetyl group from acetyl-CoA to a glyceryl hydroxyl of HepG, giving the acetylated carrier Ac-HepG. YvoF was identified by screening a B. subtilis knockout library for loss of acetylation, and is a close relative of maltose O-acetyltransferase; the two overlap partly in vitro but maltose O-acetyltransferase does not complement a yvoF knockout in vivo, so the activity is YvoF's own physiological role. Mono-acetylated species on C1 or C2 and a diacetylated species can all be formed.

Annotons

YvoF-related acetyltransferase subfamily: HepG O-acetyltransferase
hepg_acetyltransferase
Participant: Family: YvoF-related hexapeptide-repeat acetyltransferase subfamily
Family:
YvoF-related hexapeptide-repeat acetyltransferase subfamilyPANTHER:PTHR43300:SF6 Hexapeptide-repeat (LbetaH) acetyltransferase, Pfam PF00132, closely related to maltose O-acetyltransferase. The subfamily is named for YvoF itself, which is the appropriate grounding level: the parent family contains maltose O-acetyltransferases that do not substitute for YvoF in vivo.
Representative Members: yvoF (Bacillus subtilis exemplar)UniProtKB:O34993

Function

heptaprenylglycerol O-acetyltransferase activity (acetyl-CoA-dependent)GO:0016413 The broadest apt GO term. No substrate-specific term exists for O-acetylation of a prenyl glycerol ether lipid, and the chemistry is transfer to a hydroxyl, not to a nitrogen.
Substrates: heptaprenylglycerol (HepG) acetyl-CoACHEBI:57288
Products: acetylated heptaprenylglycerol (Ac-HepG) coenzyme ACHEBI:57287

Processes

ether lipid biosynthetic processGO:0008611

Locations

plasma membraneGO:0005886

Loads the carrier. Produces the module's output, the high-energy acetyl donor Ac-HepG.

Part 5: Delivery of the carried acetyl group to a lipoprotein (optional)

Marked optional because PcrB has a broader strain distribution than LhaT, and some species encoding both do not make acetylated lipoprotein. Inactive LhaT alleles are demonstrated in B. anthracis, whereas the precise defect in other B. cereus-group members is unresolved. The carrier steps can therefore run in genomes where this consumer is absent or inactive, and Ac-HepG may have further uses. Keeping the step inside the module (rather than treating it purely as downstream biology) is what makes the pathway's purpose explicit: the module's real product is a transferred acetyl group, and the carrier is regenerated.

Lipoprotein N-acetylation from Ac-HepG (LhaT/YpjA)Reactionlipoprotein_acetyl_transfer

LhaT, a polytopic membrane protein formerly annotated only as uncharacterized YpjA, transfers the acetyl group from Ac-HepG to the alpha-amino group of the N-terminal cysteine of a mature diacylglyceryl lipoprotein, giving acetylated lipoprotein (Ac-LP) and releasing HepG for reloading. The acceptor is produced by Lgt diacylglyceryl transfer and LspA signal-peptide cleavage, which are modelled in bacterial_lipoprotein_maturation and are not repeated here. How Ac-HepG reaches the outer leaflet is unknown.

Annotons

LhaT (DUF1405) family: lipoprotein heptaprenylglyceryl N-acetyltransferase
lipoprotein_n_acetyltransferase
Participant: Family: lipoprotein heptaprenylglyceryl N-acetyltransferase (LhaT/YpjA, DUF1405) family
Family:
lipoprotein heptaprenylglyceryl N-acetyltransferase (LhaT/YpjA, DUF1405) familyPANTHER:PTHR40042:SF1 Pfam PF07187 (DUF1405) integral membrane proteins, predicted to have six transmembrane helices. The N-acetyltransferase function is established for the B. subtilis member; family membership alone does not imply the activity, since LhaT is pseudogenized by poly-tyrosine insertion in Bacillus anthracis isolates and some orthologue-bearing species do not make acetylated lipoprotein.
Representative Members: lhaT/ypjA (Bacillus subtilis exemplar)UniProtKB:P54392
Required Function:
lipid-donor-dependent lipoprotein N-acetyltransferaseGO:0008080 Requires demonstrated transfer from an acetylated prenyl glycerol lipid to a lipoprotein N terminus. A DUF1405 family match or generic acetyltransferase activity is insufficient.

Function

lipoprotein N-terminal N-acetyltransferase activity, using acetylated heptaprenylglycerol as donorGO:0008080 GO:0004596 protein-N-terminal amino-acid acetyltransferase activity was checked and rejected: its definition fixes acetyl-CoA as the donor, whereas LhaT uses the lipid Ac-HepG. GO:0008080 is the nearest term that does not misstate the donor.
Substrates: acetylated heptaprenylglycerol (Ac-HepG) diacylglyceryl lipoprotein (DA-LP)
Products: N-acetylated lipoprotein (Ac-LP) heptaprenylglycerol (HepG)
Targets: bacterial lipoprotein N-terminal cysteine alpha-amino group

Processes

N-terminal protein amino acid acetylationGO:0006474 lipoprotein biosynthetic processGO:0042158

Locations

plasma membraneGO:0005886

Consumes the carrier's acetyl group and regenerates HepG, which is what makes the upstream steps a catalytic cycle rather than a lipid-accumulating pathway.