Erythromycin A biosynthesis (Saccharopolyspora erythraea)

Representative-species module for biosynthesis of the macrolide antibiotic erythromycin A in Saccharopolyspora erythraea, encoded by the ery cluster (MIBiG BGC0000055). It is grounded to the concrete S. erythraea gene set reviewed under genes/SACEN/. The module combines a modular type I polyketide synthase (DEBS) that builds the macrolactone, post-PKS cytochrome-P450 oxidations, two TDP-deoxysugar pathways feeding two glycosyltransferases, final O-methylation, and rRNA-methylation self-resistance. Companion prose/MIBiG-alignment notes are in terms/erythromycin_biosynthesis/.

MODULE:erythromycin_biosynthesisDRAFTMetabolic Pathwaymodules/erythromycin_biosynthesis.yaml

erythromycin biosynthetic processGO:1901115

MIBiG:BGC0000055

Erythromycin biosynthetic gene cluster

The ery cluster (23 genes) encodes the enzymes of erythromycin A biosynthesis in S. erythraea.

GO:1901115

erythromycin biosynthetic process

The module is grounded in the GO biological process term for erythromycin biosynthesis.

9Nodes

8Parts

0Variant Sets

0Variants

20Annotons

6Connections

Derived QC

Recommended-field compliance

25.0% recommended fields populated

references[0] · findings (0/1)
references[1] · findings (0/1)
references[2] · findings (0/1)

Module deep research

✓ present

erythromycin_biosynthesis-deep-research-falcon.md (falcon)

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 (20/20 grounded genes reviewed)

14 complete review(s) · 0 with deep research · 0 missing review · 20 reviewed but lacking deep research

Gene	Review	Complete	Deep research
A4F7P6 A4F7P6	✓	✓	✗
ermE P07287	✓	✓	✗
eryAI A4F7N8	✓	✓	✗
eryAII A4F7P0	✓	✓	✗
eryAIII A4F7P1	✓	✓	✗
eryBII A4F7P4	✓	✓	✗
eryBIII A4F7P8	✓	0/0	✗
eryBIV A4F7N7	✓	0/0	✗
eryBV A4F7N6	✓	✓	✗
eryBVI A4F7N4	✓	✓	✗
eryBVII A4F7N1	✓	✓	✗
eryCI P14290	✓	✓	✗
eryCII A4F7P2	✓	✓	✗
eryCIII A4F7P3	✓	✓	✗
eryCIV A4F7N3	✓	2/3	✗
eryCV A4F7N2	✓	4/5	✗
eryCVI A4F7N5	✓	0/0	✗
eryF Q00441	✓	✓	✗
eryG A4F7P5	✓	✓	✗
eryK P48635	✓	9/10	✗

Details

Context

Saccharopolyspora erythraea NRRL 2338NCBITaxon:405948

Erythromycin A biosynthesisMetabolic Pathwayerythromycin_biosynthesis

erythromycin biosynthetic processGO:1901115

Context

Saccharopolyspora erythraea NRRL 2338NCBITaxon:405948

Status DRAFT. EryCIV/EryCV catalytic specifics and several mycarose-pathway steps are name-/homology-based (TrEMBL) and carried as UNDECIDED in the per-gene reviews. EC 2.4.1.278 (desosaminyltransferase), EC 1.14.15.35 (EryF) and EC 1.14.13.154 (EryK) lack specific GO MF terms; the function descriptors above carry the precise activity names. See genes/SACEN/<gene>/ for per-gene reviews and terms/erythromycin_biosynthesis/ for the MIBiG-aligned prose and discrepancy notes.

Connections

debs_assembly -> eryF_step Provides Input For

6-deoxyerythronolide B is the substrate of EryF.

eryF_step -> eryBV_step Provides Input For

Erythronolide B is the acceptor for mycarosylation.

eryBV_step -> eryCIII_step Provides Input For

3-O-mycarosyl-erythronolide B is the acceptor for desosaminylation.

eryCIII_step -> tailoring Provides Input For

Erythromycin D is the substrate for the final EryK/EryG tailoring.

mycarose_pathway -> eryBV_step Provides Input For

Supplies the TDP-L-mycarose glycosyl donor.

desosamine_pathway -> eryCIII_step Provides Input For

Supplies the TDP-D-desosamine glycosyl donor.

Part 1: macrolactone assembly

DEBS modular type I PKS assembles 6-deoxyerythronolide BMetabolic Pathwaydebs_assembly

Three multimodular polypeptides (EryAI/AII/AIII) condense one propionyl-CoA starter with six (2S)-methylmalonyl-CoA extenders over six modules; the EryAIII C-terminal thioesterase macrolactonizes and releases 6-deoxyerythronolide B (6-dEB).

Annotons

DEBS1 (loading didomain + modules 1-2)

eryAI_fn

Participant: Gene: eryAI

Gene:

eryAIUniProtKB:A4F7N8

Function

erythronolide synthase activity (EC 2.3.1.94)GO:0047879

Substrates: propionyl-CoA (2S)-methylmalonyl-CoA

Loads the propionyl starter and performs the first two chain-extension cycles.

DEBS2 (modules 3-4)

eryAII_fn

Participant: Gene: eryAII

Gene:

eryAIIUniProtKB:A4F7P0

Function

erythronolide synthase activity (EC 2.3.1.94)GO:0047879

Chain-extension and beta-keto reduction cycles 3-4 (module 4 fully reducing).

DEBS3 (modules 5-6 + thioesterase)

eryAIII_fn

Participant: Gene: eryAIII

Gene:

eryAIIIUniProtKB:A4F7P1

Function

erythronolide synthase activity (EC 2.3.1.94)GO:0047879

Products: 6-deoxyerythronolide B

Final extensions; the thioesterase macrolactonizes and releases 6-dEB.

type II thioesterase (PKS editing/proofreading)

teII_fn

Participant: Gene: TEII (locus CAM00070)

Gene:

TEII (locus CAM00070)UniProtKB:A4F7P6

Function

acyl-[ACP] hydrolase, PKS editingGO:0016297

Hydrolyzes aberrant acyl-ACP species to maintain assembly-line fidelity.

Part 2: post-PKS C-6 hydroxylation

EryF hydroxylates 6-dEB to erythronolide BReactioneryF_step

Annotons

6-deoxyerythronolide B C-6 hydroxylase (P450eryF)

eryF_fn

Participant: Gene: eryF

Gene:

eryFUniProtKB:Q00441

Function

6-deoxyerythronolide B 6-hydroxylase activity (EC 1.14.15.35)GO:0004497

Substrates: 6-deoxyerythronolide B dioxygen

Products: erythronolide B

Locations

cytoplasmGO:0005737

Part 3: mycarosylation (first glycosylation)

EryBV attaches L-mycarose to erythronolide BReactioneryBV_step

Annotons

mycarosyltransferase

eryBV_fn

Participant: Gene: eryBV

Gene:

eryBVUniProtKB:A4F7N6

Function

TDP-L-mycarose mycarosyltransferase activityGO:0016758

Substrates: erythronolide B TDP-L-mycarose

Products: 3-O-mycarosyl-erythronolide B

Part 4: desosaminylation (second glycosylation, activator-dependent)

EryCIII (activated by EryCII) attaches D-desosamine, forming erythromycin DReactioneryCIII_step

Annotons

desosaminyltransferase

eryCIII_fn

Participant: Gene: eryCIII

Gene:

eryCIIIUniProtKB:A4F7P3

Function

3-alpha-mycarosylerythronolide B desosaminyltransferase activity (EC 2.4.1.278)GO:0016758

Substrates: 3-O-mycarosyl-erythronolide B TDP-D-desosamine

Products: erythromycin D

EryCII - required allosteric activator of EryCIII (heme-less P450 pseudoenzyme)

eryCII_fn

Participant: Gene: eryCII

Gene:

eryCIIUniProtKB:A4F7P2

Function

glycosyltransferase (EryCIII) activator activityGO:0008047

Forms an alpha2-beta2 heterotetramer with EryCIII and is required for its activity; a cytochrome-P450 homologue that lacks the heme and is catalytically dead.

Part 5: final tailoring to erythromycin A

C-12 hydroxylation (EryK) and 3''-O-methylation (EryG)Metabolic Pathwaytailoring

EryK (C-12 hydroxylation) and EryG (mycarose 3''-O-methylation to cladinose) act in either order on erythromycin D, via erythromycins B and C, converging on erythromycin A.

Annotons

erythromycin C-12 hydroxylase (CYP113A1)

eryK_fn

Participant: Gene: eryK

Gene:

eryKUniProtKB:P48635

Function

erythromycin 12-hydroxylase activity (EC 1.14.13.154)GO:0016709

Substrates: erythromycin D dioxygen

Products: erythromycin C

erythromycin 3''-O-methyltransferase (mycarose to cladinose)

eryG_fn

Participant: Gene: eryG

Gene:

eryGUniProtKB:A4F7P5

Function

erythromycin 3''-O-methyltransferase activity (EC 2.1.1.254)GO:0102307

Substrates: erythromycin C S-adenosyl-L-methionine

Products: erythromycin A S-adenosyl-L-homocysteine

Part 6: TDP-D-desosamine biosynthesis (donor for desosaminylation)

TDP-D-desosamine biosynthesis (EryC* + EryBVII)Metabolic Pathwaydesosamine_pathway

Builds the aminodeoxysugar donor TDP-D-desosamine from a TDP-4-keto-6-deoxyglucose precursor. Several enzymes are minimally characterized; the C-3 aminotransferase (EryCI) and the N,N-dimethyltransferase (EryCVI) are the best-defined steps.

Annotons

PLP-dependent sugar aminotransferase (DegT/DnrJ/EryC1 family)

eryCI_fn

Participant: Gene: eryCI

Gene:

eryCIUniProtKB:P14290

Function

sugar (C-3) aminotransferase activityGO:0008483

Installs the C-3 amino group; UniProt P14290 is mis-named a "sensory transduction protein".

PLP-dependent 3,4-dehydratase (activity unverified)

eryCIV_fn

Participant: Gene: eryCIV

Gene:

eryCIVUniProtKB:A4F7N3

Function

pyridoxal phosphate bindingGO:0030170

radical-SAM (4Fe-4S) enzyme (activity unverified)

eryCV_fn

Participant: Gene: eryCV

Gene:

eryCVUniProtKB:A4F7N2

Function

4Fe-4S cluster binding (radical-SAM)GO:0051539

TDP-desosamine N,N-dimethyltransferase

eryCVI_fn

Participant: Gene: eryCVI

Gene:

eryCVIUniProtKB:A4F7N5

Function

TDP-desosamine N,N-dimethyltransferase activityGO:0008168

Products: TDP-D-desosamine

dTDP-sugar 3,5-epimerase (shared)

eryBVII_desosamine_fn

Participant: Gene: eryBVII

Gene:

eryBVIIUniProtKB:A4F7N1

Function

dTDP-sugar 3,5-epimerase activity (EC 5.1.3.13)GO:0008830

Shared 3,5-epimerase used by both the desosamine and mycarose branches.

Part 7: TDP-L-mycarose biosynthesis (donor for mycarosylation)

TDP-L-mycarose biosynthesis (EryB*)Metabolic Pathwaymycarose_pathway

Builds the branched-chain deoxysugar donor TDP-L-mycarose. Enzymes are largely name-/homology-defined (TrEMBL); the C-methyltransferase (EryBIII) installs the C-3 methyl branch.

Annotons

2,3-dehydratase

eryBVI_fn

Participant: Gene: eryBVI

Gene:

eryBVIUniProtKB:A4F7N4

Function

NDP-4-keto-6-deoxyglucose 2,3-dehydratase activityGO:0016829

TDP-sugar 2,3-reductase

eryBII_fn

Participant: Gene: eryBII

Gene:

eryBIIUniProtKB:A4F7P4

Function

TDP-4-keto-6-deoxyhexose 2,3-reductase activityGO:0016491

3-C-methyltransferase (mycarose C-methyl branch)

eryBIII_fn

Participant: Gene: eryBIII

Gene:

eryBIIIUniProtKB:A4F7P8

Function

NDP-4-keto-2,6-dideoxyhexose 3-C-methyltransferase activityGO:0008168

4-reductase

eryBIV_fn

Participant: Gene: eryBIV

Gene:

eryBIVUniProtKB:A4F7N7

Function

dTDP-4-keto-6-deoxy-L-hexose 4-reductase activityGO:0016491

Products: TDP-L-mycarose

Part 8: self-resistance (optional)

ErmE 23S rRNA methylation self-resistanceReactionresistance

Annotons

23S rRNA A2085 N6,N6-dimethyltransferase

ermE_fn

Participant: Gene: ermE

Gene:

ermEUniProtKB:P07287

Function

23S rRNA (adenine-2085-N6)-dimethyltransferase activity (EC 2.1.1.184)GO:0052910

Dimethylates 23S rRNA A2085 (E. coli A2058), blocking erythromycin binding to the 50S subunit and conferring macrolide self-resistance on the producer.