9WQW

aminoacyl-tRNA-dependent peptide synthase, Sbb17

Summary for 9WQW

• Entry DOI: 10.2210/pdb9wqw/pdb
• Descriptor: aminoacyl-tRNA-dependent peptide synthase, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: aminoacyl-trna-dependent peptide synthase, sbb17, transferase
• Biological source: Streptomyces prunicolor
• Total number of polymer chains: 1
• Total formula weight: 34439.57

Authors

Nakashima, Y.,Sherif, H.A.M.A.,Maruyama, C.,Morita, H.,Hamano, Y. (deposition date: 2025-09-11, release date: 2026-04-01)

Primary citation

Maruyama, C.,Nakashima, Y.,Matsuda, K.,A Hamdy, S.,Uchiyama, S.,Goto, Y.,Mori, T.,Ogasawara, Y.,Shin-Ya, K.,Abe, I.,Dairi, T.,Suga, H.,Morita, H.,Hamano, Y.
tRNA-Dependent Chemoenzymatic Transformation of Aminoacyl Pendant Moieties of Streptothricin Antibiotics.
J.Am.Chem.Soc., 2026

PubMed Abstract: Streptothricin (ST) antibiotics are promising agents against multidrug-resistant pathogens and are structurally classified into two groups, containing either a β-lysyl or a glycyl pendant moiety attached via an amide bond to an amino sugar core. These pendant moieties are essential determinants of the biological activity and selective toxicity of ST antibiotics. We previously demonstrated that during ST biosynthesis, the β-lysyl pendant moiety is installed by nonribosomal peptide synthetases, whereas the glycyl pendant moiety is generated by a Gly-tRNA-dependent amide-forming enzyme. Here, we present a chemoenzymatic approach to transform aminoacyl pendant moieties using the promiscuous tRNA-dependent amide-forming enzyme Sba18. Remarkably, Sba18 generates two new ST derivatives, alanylthricin and serylthricin, by utilizing Ala-tRNA and Ser-tRNA, respectively. Moreover, Sba18 accepts aminoacyl-tRNA mimics prepared by flexizyme-mediated charging of chemically synthesized aminoacyl groups and produces additional 11 ST derivatives. Alanylthricin and serylthricin retain antibiotic activity, demonstrating that this tRNA-dependent chemoenzymatic approach provides a viable strategy for expanding the structural diversity of streptothricin antibiotics. Furthermore, structural comparison of Sba18 with its Gly-tRNA-specific orthologue Sbb17 elucidates the catalytic and substrate-recognition mechanisms underlying the broad specificity of Sba18. These structural insights provide a foundation for expanding the structural diversity not only of ST antibiotics but also of other peptide natural products biosynthesized using aminoacyl-tRNAs.

PubMed: 41823201
DOI: 10.1021/jacs.6c00367

Experimental method

X-RAY DIFFRACTION (1.96 Å)