8YXS

X-ray structure of non-heme iron dioxygenase from Aspergillus brunneoviolaceus

Summary for 8YXS

• Entry DOI: 10.2210/pdb8yxs/pdb
• Descriptor: Oxidoreductase AflY, FE (III) ION (3 entities in total)
• Functional Keywords: regioselectivity ring-opening, direction evolution, anthraquinone, xanthone, oxidoreductase
• Biological source: Aspergillus brunneoviolaceus
• Total number of polymer chains: 5
• Total formula weight: 256724.50

Authors

Lv, X.,Ma, X. (deposition date: 2024-04-02, release date: 2025-04-09, Last modification date: 2026-04-22)

Primary citation

Lv, X.J.,Ai, C.Z.,Zhang, L.R.,Ma, X.X.,Zhang, J.J.,Zhu, J.P.,Tan, R.X.
Regioselectivity switches between anthraquinone precursor fissions involved in bioactive xanthone biosynthesis.
Chem Sci, 15:19534-19545, 2024

PubMed Abstract: Xanthone-based polyketides with complex molecular frameworks and potent bioactivities distribute and function in different biological kingdoms, yet their biosynthesis remains under-investigated. In particular, nothing is known regarding how to switch between the C-C (C-selective) and C-C bond (C-selective) cleavages of anthraquinone intermediates involved in biosynthesizing strikingly different frameworks of xanthones and their siblings. Enabled by our characterization of antiosteoporotic brunneoxanthones, a subfamily of polyketides from FB-2, we present herein the brunneoxanthone biosynthetic gene cluster and the C-selective cleavage of anthraquinone (chrysophanol) hydroquinone leading ultimately to the bioactive brunneoxanthones under the catalysis of BruN (an undescribed atypical non-heme iron dioxygenase) in collaboration with BruM as a new oxidoreductase that reduces the anthraquinone into its hydroquinone using NADPH as a cofactor. The insights into the driving force that determines whether the C- or C-selective cleavages of anthraquinone hydroquinones take place were achieved by a combination of multiprotein sequence alignment, directed protein evolution, theoretical simulation, chemical capture of hydroquinone tautomer, O chasing, and X-ray crystal structure of the BruN mutant, eventually allowing for the protocol establishment for the on-demand switch between the two ways of anthraquinone openings. Collectively, the work paves the way for the synthetic biology-based regeneration of uniquely structured high-value xanthones present in low abundance in complex mixtures, and helps to deepen the understanding on why and how such xanthones and their congeners are biosynthesized by different (micro)organisms in nature.

PubMed: 39568878
DOI: 10.1039/d4sc06369d

Experimental method

X-RAY DIFFRACTION (3.62 Å)