9LSD

Crystal structure of a polyketide cyclase FasU from Streptomyces kanamyceticus

Summary for 9LSD

• Entry DOI: 10.2210/pdb9lsd/pdb
• Descriptor: Antibiotic biosynthesis monooxygenase, 2-(2-ETHOXYETHOXY)ETHANOL, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: polyketide, cyclase, biosynthetic protein
• Biological source: Streptomyces kanamyceticus
• Total number of polymer chains: 2
• Total formula weight: 27939.16

Authors

Luo, S.,Zhu, C. (deposition date: 2025-02-04, release date: 2025-03-12)

Primary citation

Jiang, K.,Zhu, C.,Yan, X.,Li, G.,Lin, Z.,Deng, Z.,Luo, S.,Qu, X.
A Stereoselective Decarboxylative Aromatase/Cyclase Directs the Biosynthesis of an Axially Chiral Biphenyl Framework in Fasamycin.
J.Am.Chem.Soc., 147:5596-5601, 2025

PubMed Abstract: Aromatic polyketides are an important class of natural products with various bioactivities, and their structural diversity arises from modifications to their aromatic frameworks. In this study, we identify a stereoselective aromatase/cyclase (ARO/CYC) FasU, which is responsible for forming the axial chiral biphenyl framework in fasamycin. FasU catalyzes sequential decarboxylation and cyclization/aromatization with strict -stereospecificity on a previously unidentified biosynthetic intermediate. Through crystal structure analysis and site-directed mutagenesis, we reveal the enzyme's substrate binding mode, stereospecificity, and the key residues involved in catalysis. This discovery introduces a novel class of ARO/CYC enzymes in type II polyketide biosynthesis, advancing the development of biocatalysts for chiral aromatic polyketides.

PubMed: 39910892
DOI: 10.1021/jacs.4c18376

Experimental method

X-RAY DIFFRACTION (2.01 Å)