5Z4F

An anthrahydroquino-Gama-pyrone synthase Txn09 complexed with SUM

Summary for 5Z4F

• Entry DOI: 10.2210/pdb5z4f/pdb
• Descriptor: TxnO9, 1,8-dihydroxy-2-[(4R)-4-hydroxy-4-methyl-3-oxohexanoyl]-3-methylanthracene-9,10-dione (2 entities in total)
• Functional Keywords: type ii polyketide heterocyclase, enzyme mechanism, natural product, streptomyces bottropensis, biosynthetic protein
• Biological source: Streptomyces bottropensis
• Total number of polymer chains: 1
• Total formula weight: 18234.33

Authors

Song, Y.J.,Cao, C.Y. (deposition date: 2018-01-11, release date: 2019-01-30, Last modification date: 2024-05-15)

Primary citation

Hou, X.F.,Song, Y.J.,Zhang, M.,Lan, W.X.,Meng, S.,Wang, C.X.,Pan, H.X.,Cao, C.Y.,Tang, G.L.
Enzymology of Anthraquinone-gamma-Pyrone Ring Formation in Complex Aromatic Polyketide Biosynthesis.
Angew. Chem. Int. Ed. Engl., 57:13475-13479, 2018

PubMed Abstract: Aromatic-fused γ-pyrones are structural features of many bioactive natural products and valid scaffolds for medicinal chemistry. However, the enzymology of their formation has not been completely established. Now it is demonstrated that TxnO9, a CalC-like protein belonging to a START family, functions as an unexpected anthraquinone-γ-pyrone synthase involved in the biosynthesis of antitumor antibiotic trioxacarcin A (TXN-A). Structural analysis by NMR identified a likely substrate/product-binding mode and putative key active sites of TxnO9, which allowed an enzymatic mechanism to be proposed. Moreover, a subset of uncharacterized homologous proteins bearing an unexamined Lys-Thr dyad exhibit the same function. Therefore, the functional assignment and mechanistic investigation of this γ-pyrone synthase elucidated an undescribed step in TXN-A biosynthesis, and the discovery of this new branch of polyketide heterocyclases expands the functions of the START superfamily.

PubMed: 30151879
DOI: 10.1002/anie.201806729

Experimental method

SOLUTION NMR