9LMM

An antibiotic biosynthesis monooxygenase family protein from Streptomyces sp. MA37

Summary for 9LMM

• Entry DOI: 10.2210/pdb9lmm/pdb
• Descriptor: Antibiotic biosynthesis monooxygenase (2 entities in total)
• Functional Keywords: polyketide, carboxyl-protecting enzyme, antibiotic
• Biological source: Streptomyces sp. MA37
• Total number of polymer chains: 2
• Total formula weight: 24995.70

Authors

Jiang, K.,Qu, X.D. (deposition date: 2025-01-19, release date: 2025-11-26)

Primary citation

Jiang, K.,Zhu, C.,Gao, Y.,Dai, Y.,Yan, X.,Yang, L.,Jiang, M.,Lin, Z.,Deng, Z.,Luo, S.,Qu, X.
Terminal Carboxyl Editing Drives Divergence in Fasamycin and Anthrabenzoxocinone Biosynthesis.
J.Am.Chem.Soc., 147:26468-26476, 2025

PubMed Abstract: Aromatic polyketides are a vast category of natural products known for their wide-ranging biological activities, with their structural variety stemming from modifications to their core frameworks. This study reveals two distinct processes that shape the frameworks of (+)/(-)-anthrabenzoxocinone (ABX) and fasamycin (FAS) from a common biosynthetic precursor, compound . FasS protects the carboxyl group of this molecule without altering it, preparing it for FasU, which then crafts FAS's unique, nonplanar axial chiral aromatic framework. In contrast, AbxO and AbxO remove the carboxyl group from compound , producing phenyldimethylanthrone (PDA), a key intermediate for (+)/(-)-ABX formation. Structural analysis of AccS (1.65 Å, FasS homologue) and AbxO (1.99 Å), combined with mutagenesis studies, identifies key residues of AccS and AbxO, providing insights into the carboxyl-protecting mechanism and decarboxylation mechanism. Evolutionary and functional studies further connect AccS and AbxO to the N- and C-termini of the long-studied, functionally enigmatic protein family, WhiE-ORFI (resolved in 2.3 Å). This study unveils hidden strategies for terminal carboxyl group editing, providing new insights into the origins of aromatic polyketide diversity.

PubMed: 40690660
DOI: 10.1021/jacs.5c06089

Experimental method

X-RAY DIFFRACTION (1.65 Å)