8IS2

Crystal structure of a polyketide aromatase/cyclase Abx(+)D from Actinomycetes sp. MA7150.

Summary for 8IS2

• Entry DOI: 10.2210/pdb8is2/pdb
• Descriptor: Cyclase (2 entities in total)
• Functional Keywords: aromatase, cyclase, polyketide, biosynthetic protein
• Biological source: uncultured actinomycete
• Total number of polymer chains: 2
• Total formula weight: 26880.20

Authors

Luo, S.,Chen, X. (deposition date: 2023-03-20, release date: 2024-02-28, Last modification date: 2024-03-20)

Primary citation

Jiang, K.,Chen, X.,Yan, X.,Li, G.,Lin, Z.,Deng, Z.,Luo, S.,Qu, X.
An unusual aromatase/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin.
Proc.Natl.Acad.Sci.USA, 121:e2321722121-e2321722121, 2024

PubMed Abstract: Aromatic polyketides are renowned for their wide-ranging pharmaceutical activities. Their structural diversity is mainly produced via modification of limited types of basic frameworks. In this study, we characterized the biosynthesis of a unique basic aromatic framework, phenyldimethylanthrone (PDA) found in (+)/(-)-anthrabenzoxocinones (ABXs) and fasamycin (FAS). Its biosynthesis employs a methyltransferase (AbxM/AbxM/FasT) and an unusual TcmI-like aromatase/cyclase (ARO/CYC, AbxD/AbxD/FasL) as well as a nonessential helper ARO/CYC (AbxC/AbxC/FasD) to catalyze the aromatization/cyclization of polyketide chain, leading to the formation of all four aromatic rings of the PDA framework, including the C9 to C14 ring and a rare angular benzene ring. Biochemical and structural analysis of AbxD reveals a unique loop region, giving rise to its distinct acyl carrier protein-dependent specificity compared to other conventional TcmI-type ARO/CYCs, all of which impose on free molecules. Mutagenic analysis discloses critical residues of AbxD for its catalytic activity and indicates that the size and shape of its interior pocket determine the orientation of aromatization/cyclization. This study unveils the tetracyclic and non-TcmN type C9 to C14 ARO/CYC, significantly expanding our cognition of ARO/CYCs and the biosynthesis of aromatic polyketide framework.

PubMed: 38446858
DOI: 10.1073/pnas.2321722121

Experimental method

X-RAY DIFFRACTION (1.32 Å)