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- EMDB-64929: Cryo-EM structure of the multi-component acyltransferase complex ... -

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Basic information

Entry
Database: EMDB / ID: EMD-64929
TitleCryo-EM structure of the multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2
Map data
Sample
  • Complex: The multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2
    • Protein or peptide: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein
    • Protein or peptide: 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein
    • Protein or peptide: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein
  • Ligand: ZINC ION
Keywordsenzyme complex / thiolase / Friedel-Crafts acylation / biosynthesis / TRANSFERASE
Function / homology
Function and homology information


secondary metabolite biosynthetic process / acyltransferase activity, transferring groups other than amino-acyl groups / acyltransferase activity
Similarity search - Function
Domain of unknown function DUF35, rubredoxin-like zinc ribbon domain, N-terminal / : / ChsH2, rubredoxin-like zinc ribbon domain / : / Thiolase C-terminal domain-like / 3-Oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal / 3-Oxoacyl-[acyl-carrier-protein (ACP)] synthase III C terminal / Thiolase / Thiolase-like / Nucleic acid-binding, OB-fold
Similarity search - Domain/homology
2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein / 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein / 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein
Similarity search - Component
Biological speciesStreptococcus macacae (bacteria) / Streptococcus macacae NCTC 11558 (bacteria)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.16 Å
AuthorsLuo Z / Shen Z / Liao G / Tang X / Pan X
Funding support China, 3 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32322039 China
National Natural Science Foundation of China (NSFC)32401633 China
National Natural Science Foundation of China (NSFC)82173719 China
CitationJournal: Nat Commun / Year: 2026
Title: Evolutionary repurposing of a metabolic thiolase complex enables antibiotic biosynthesis.
Authors: Ge Liao / Ruolan Sun / Zilin Shen / Zhiteng Luo / Cuiping Pang / Zhuanglin Shen / Anfu Wei / Chengneng Mi / Gengfan Wu / Fengfang Li / Yong-Xin Li / Kin Kuan Hoi / Xiaojing Pan / Xiaoyu Tang /
Abstract: The functional diversification of biosynthetic enzymes underlies the chemical richness of natural products, yet how primary metabolic enzymes evolve to acquire specialized functions in secondary ...The functional diversification of biosynthetic enzymes underlies the chemical richness of natural products, yet how primary metabolic enzymes evolve to acquire specialized functions in secondary metabolism remains elusive. Here, we report a tripartite enzyme complex from oral Streptococcus species-comprising 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS), acetyl-CoA acetyltransferase (ACAT), and a DUF35 protein-that catalyzes an unusual Friedel-Crafts C-acetylation on a pyrrolidine-2,4-dione scaffold, completing the biosynthesis of the antibiotic reutericyclin A. Cryo-electron microscopy of the S. macacae-derived thiolase complex (SmaATase) reveals a conserved architecture resembling the archaeal HMGS/ACAT/DUF35 complex involved in the mevalonate pathway, yet with key catalytic residues rewired to reprogram substrate specificity. Biochemical characterization, molecular modeling, and evolutionary analysis confirmed that the ancestral activity of HMG-CoA synthesis has been lost, while the complex has been repurposed to mediate Friedel-Crafts C-acylation of small molecule acceptors. These findings reveal a rare example of thiolase complex neofunctionalization, shedding light on an underexplored trajectory in enzyme evolution and offering a template for engineering C-C bond-forming catalysts in synthetic biology.
History
DepositionJun 4, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateFeb 11, 2026-
Current statusFeb 11, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_64929.png

Downloads & links

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Map

FileDownload / File: emd_64929.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 256 pix.
= 237.312 Å		0.93 Å/pix.
x 256 pix.
= 237.312 Å		0.93 Å/pix.
x 256 pix.
= 237.312 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.927 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.23
Minimum - Maximum-1.6181813 - 2.6356938
Average (Standard dev.)0.0008029527 (±0.09970758)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 237.312 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_64929_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_64929_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : The multi-component acyltransferase complex MucABC from Streptoco...

EntireName: The multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2
Components
  • Complex: The multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2
    • Protein or peptide: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein
    • Protein or peptide: 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein
    • Protein or peptide: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein
  • Ligand: ZINC ION

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Supramolecule #1: The multi-component acyltransferase complex MucABC from Streptoco...

SupramoleculeName: The multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Streptococcus macacae (bacteria)

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Macromolecule #1: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal d...

MacromoleculeName: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Streptococcus macacae NCTC 11558 (bacteria)
Molecular weightTheoretical: 39.905977 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGNKQIGIKS YGISIPYFRL PVEETIKVWN NNNVDYIKNK IGVKRRTVVS SDEDTLTLAM EAGQEAVLHF KEDVAKIDSI LLGSCTTPD IFKSNANQLM SFLFNKNDYF GCDIRASENS GAASLVLGYS LVSSGLSNTS LIFSADTLSK NIFPSELREP Y IGSGAASI ...String:
MGNKQIGIKS YGISIPYFRL PVEETIKVWN NNNVDYIKNK IGVKRRTVVS SDEDTLTLAM EAGQEAVLHF KEDVAKIDSI LLGSCTTPD IFKSNANQLM SFLFNKNDYF GCDIRASENS GAASLVLGYS LVSSGLSNTS LIFSADTLSK NIFPSELREP Y IGSGAASI ILGKGEDILA EIIGIGNSNA SFPEQGRTED NRYLRVLANL NYSVVKEGRI KRSLESINNA LENASLKAED IK YFVFQDG TEQTYKEFSH FFHFDNVINQ DIFKNLGYIG SASPIISMLA ALENAEVGDI ILMCGYGHSS GSTTVIFRVT EEI TFKNKI IDKLKNYKDI NYSEAMKHEF KYSQPEISLG TFI

UniProtKB: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein

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Macromolecule #2: 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein

MacromoleculeName: 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein
type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Streptococcus macacae NCTC 11558 (bacteria)
Molecular weightTheoretical: 16.954482 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MFSNEQISNP TIESSLKDWR EQGGLTRLEG SKCPHCDELF YPRRFVCPYC FCRSLKTYKF SGMGKIKNIE INSISQVAVI GYREISPRY LSVIELAEGV DVLGEIIECS EIESIHSLIG REVMSVVRKQ SRSGNTSWKY GYKFKLKEG

UniProtKB: 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein

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Macromolecule #3: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein

MacromoleculeName: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein
type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Streptococcus macacae NCTC 11558 (bacteria)
Molecular weightTheoretical: 44.574516 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGIKIQVSGV GCTNAPGLPH INKSFKELLV EAAYKALEDA FLSPHLIDGA SFSYAGEGEI GHGGIVPTLV DALGLAPLEG YINIGN(SCY)AS SHMALLQGCE MIESGRYRHV LVAGFDKMTD ILPFENYMLM STDSLYDYNL GFSHIDAFLL QQEYISK YG IQPIKLKEAL ...String:
MGIKIQVSGV GCTNAPGLPH INKSFKELLV EAAYKALEDA FLSPHLIDGA SFSYAGEGEI GHGGIVPTLV DALGLAPLEG YINIGN(SCY)AS SHMALLQGCE MIESGRYRHV LVAGFDKMTD ILPFENYMLM STDSLYDYNL GFSHIDAFLL QQEYISK YG IQPIKLKEAL LKFSTLMKKY GAVNKVSSNF GKELPTSKEL ENQPFFGNAM SAGEGASAVI LSAMEANNKN SSQEKVII A GRGYTNTSHY IPHRYKEKLL HHKNKDSNDE VGMFNGIPLE LSINQAYSEA KISAKDLNIL ELYDQGLNSF ISMEAAGIC PKGEAIEYIC NGGGTIDSSV AINTDGGNIA RGHAGGGASL YQIIEIVKQL QGRASGMQIK KRQYGLSTVI GGAYATAAAI VLKNEEYLE HHHHHH

UniProtKB: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein

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Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration4 mg/mL
BufferpH: 7.4
GridModel: Quantifoil / Material: GOLD / Mesh: 400
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.16 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 1155067
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final 3D classificationSoftware - Name: cryoSPARC
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
Output model

PDB-9vbo:
Cryo-EM structure of the multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:2:2

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