Recombinant versus native botulinum neurotoxin type A: structural and pharmacodynamic comparison
- 1Chongqing Claruvis Pharmaceutical Co., Ltd, No. 28 Yuefu Avenue, DaDi (International) Life Science Park, A2, Beibei District, Chongqing400700, People’s Republic of China
- 2WuXi Biologics Biosafety Testing (Shanghai) Co., Ltd, No. 860 Xinyang Road, Lin’gang District, Shanghai Pilot Free Trade, People’s Republic of China
Abstract
Botulinum neurotoxins (BoNTs) are highly potent exotoxins utilized for esthetic and therapeutic indications. Unlike traditional products derived from Clostridium botulinum, this study presents the design, production, structural characterization and preclinical pharmacodynamics of recombinant BoNT type A1 (rBoNT/A, YY001), newly approved by the National Medical Products Administration and the first rBoNT/A product to be licensed for commercialization in the world. Expressed in Escherichia coli and purified to greater than 99% homogeneity, YY001 shares a core amino-acid sequence with BoNT/A1 in Botox. The additional five residues at the N-terminus and six residues at the C-terminus of the light chain (LC), as well as two residues at the N-terminus of the heavy chain (HC), originate from residual amino acids after protease cleavage; mass-spectrometric peptide mapping confirmed this sequence fidelity. Cryo-electron microscopy yields a 3.2 Å resolution map of the full-length active rBoNT/A, revealing a canonical LC–HN–HC three-domain architecture that predominantly adopts an open conformation, with a root-mean-square deviation of 1.3–1.5 Å relative to native BoNT/A. In vivo head-to-head pharmacodynamic studies showed comparable potency between YY001 and Botox in both mouse digit abduction score assay and rat compound muscle action potential assays. Altogether, the structural, biochemical and pharmacological data indicate that YY001 possesses molecular and functional attributes that are highly comparable to those of native BoNT/A, while providing improved manufacturing consistency and reduced biosafety risks.
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BibTeX
@article{yao2026recombinant,
title = {{Recombinant versus native botulinum neurotoxin type A: structural and pharmacodynamic comparison}},
author = {Zongren Yao and Lingyi Xu and Yu Lu and Hui Gong and Xiaoyun Sun and Yaokun Zhao and Jinhuan Chen and Liming Yang and Qingqing Chen and Wu Yang},
journal = {Acta Crystallographica Section F: Structural Biology Communications},
year = {2026},
month = oct,
doi = {10.1107/s2053230x26009830},
url = {https://doi.org/10.1107/s2053230x26009830},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Recombinant versus native botulinum neurotoxin type A: structural and pharmacodynamic comparison
AU - Zongren Yao
AU - Lingyi Xu
AU - Yu Lu
AU - Hui Gong
AU - Xiaoyun Sun
AU - Yaokun Zhao
AU - Jinhuan Chen
AU - Liming Yang
AU - Qingqing Chen
AU - Wu Yang
PY - 2026
DA - 2026/10/22
JO - Acta Crystallographica Section F: Structural Biology Communications
DO - 10.1107/s2053230x26009830
UR - https://doi.org/10.1107/s2053230x26009830
AB - Botulinum neurotoxins (BoNTs) are highly potent exotoxins utilized for esthetic and therapeutic indications. Unlike traditional products derived from Clostridium botulinum, this study presents the design, production, structural characterization and preclinical pharmacodynamics of recombinant BoNT type A1 (rBoNT/A, YY001), newly approved by the National Medical Products Administration and the first rBoNT/A product to be licensed for commercialization in the world. Expressed in Escherichia coli and purified to greater than 99% homogeneity, YY001 shares a core amino-acid sequence with BoNT/A1 in Botox. The additional five residues at the N-terminus and six residues at the C-terminus of the light chain (LC), as well as two residues at the N-terminus of the heavy chain (HC), originate from residual amino acids after protease cleavage; mass-spectrometric peptide mapping confirmed this sequence fidelity. Cryo-electron microscopy yields a 3.2 Å resolution map of the full-length active rBoNT/A, revealing a canonical LC–HN–HC three-domain architecture that predominantly adopts an open conformation, with a root-mean-square deviation of 1.3–1.5 Å relative to native BoNT/A. In vivo head-to-head pharmacodynamic studies showed comparable potency between YY001 and Botox in both mouse digit abduction score assay and rat compound muscle action potential assays. Altogether, the structural, biochemical and pharmacological data indicate that YY001 possesses molecular and functional attributes that are highly comparable to those of native BoNT/A, while providing improved manufacturing consistency and reduced biosafety risks.
SN - 2053-230X
ER -