9LWESummary for 9LWE
| Entry DOI | 10.2210/pdb9lwe/pdb |
| Descriptor | P450, PROTOPORPHYRIN IX CONTAINING FE, 8H-Thieno[2,3-b]indole-2-carboxamide, ... (4 entities in total) |
| Functional Keywords | p450 hydroxylase, thnc, oxidoreductase |
| Biological source | Streptomyces sp. FXJ1.172 |
| Total number of polymer chains | 1 |
| Total formula weight | 44765.64 |
| Authors | |
| Primary citation | Shi, Y.,Zhao, X.,Pang, Z.,Zhang, X.,Xie, Y.,Chang, S.,Li, X.,Li, Y.,Li, X.,Zhang, X.,Jiang, J.,Hong, B. Distinct Oxidoreductases Orchestrate Indolethiophene Skeleton Formation and N-Hydroxylation-Mediated Bioactivation in Thienoxidolin Biosynthesis. Angew.Chem.Int.Ed.Engl., :e7072895-e7072895, 2026 Cited by PubMed Abstract: Microbial sulfur-containing secondary metabolite thienodolin (1) features a unique tricyclic thieno[2,3-b]indole scaffold, yet its biosynthesis has remained enigmatic. Here, we uncover an unexpected enzymatic logic in which a consortium of distinct oxidoreductases cooperatively orchestrates indolethiophene skeleton formation and subsequent bioactivation, ultimately generating the authentic antibacterial metabolite thienoxidolin (10). Following thiotryptophan formation by SDR enzyme TndE, the heme-dependent DUF6875 enzyme TndD initiates C-S bond formation via N-hydroxylation to yield a dearomatized tricyclic species, which is efficiently driven forward and stabilized by aromatization catalyzed by the FAD-dependent oxidoreductase TndG. Notably, TndD functions as a bidirectional redox enzyme, reverting the N-hydroxyl group to the stable N-H form to complete the indolethiophene scaffold construction. After amide formation, late-stage N-hydroxylation by the cytochrome P450 enzyme TndC, previously misassigned as the C-S bond-forming enzyme, produces the bioactive product 10. Intriguingly, TndD may also mediate the deactivation of 10 back to 1, representing an intrinsic self-protection mechanism. Together, these results expand the catalytic repertoire of heme-dependent enzymes and highlight reversible N-hydroxylation as a pivotal strategy for heterocycle formation and bioactivity regulation in microbial secondary metabolism. PubMed: 42275295DOI: 10.1002/anie.7072895 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
Download full validation report
