7VBR

Fe(II)/(alpha)ketoglutarate-dependent dioxygenase TlxI

Summary for 7VBR

• Entry DOI: 10.2210/pdb7vbr/pdb
• Descriptor: Fe(II)/(alpha)ketoglutarate-dependent dioxygenase TlxI (2 entities in total)
• Functional Keywords: fe(ii)/(alpha)ketoglutarate-dependent dioxygenase, oxidoreductase
• Biological source: Talaromyces purpureogenus
• Total number of polymer chains: 4
• Total formula weight: 126707.46

Authors

Li, X.,Awakawa, T.,Mori, T.,Abe, I. (deposition date: 2021-09-01, release date: 2022-04-20, Last modification date: 2023-11-29)

Primary citation

Li, X.,Awakawa, T.,Mori, T.,Ling, M.,Hu, D.,Wu, B.,Abe, I.
Heterodimeric Non-heme Iron Enzymes in Fungal Meroterpenoid Biosynthesis.
J.Am.Chem.Soc., 143:21425-21432, 2021

PubMed Abstract: Talaromyolides (-) are a group of unusual 6/6/6/6/6/6 hexacyclic meroterpenoids with (3)-6-hydroxymellein and 4,5-seco-drimane substructures, isolated from the marine fungus . We have identified the biosynthetic gene cluster by heterologous expression in , enzyme assays, and CRISPR-Cas9-based gene inactivation. Remarkably, the heterodimer of non-heme iron (NHI) enzymes, TlxJ-TlxI, catalyzes three steps of oxidation including a key reaction, hydroxylation at C-5 and C-9 of , the intermediate with 3-ketohydroxydrimane scaffold, to facilitate a retro-aldol reaction, leading to the construction of the 4,5-secodrimane skeleton and characteristic ketal scaffold of -. The products of TlxJ-TlxI, and , were further hydroxylated at C-4'β by another NHI heterodimer, TlxA-TlxC, and acetylated by TlxB to yield the final products, and . The X-ray structural analysis coupled with site-directed mutagenesis provided insights into the heterodimer TlxJ-TlxI formation and its catalysis. This is the first report to show that two NHI proteins form a heterodimer for catalysis and utilizes a novel methodology to create functional oxygenase structures in secondary metabolite biosynthesis.

PubMed: 34881885
DOI: 10.1021/jacs.1c11548

Experimental method

X-RAY DIFFRACTION (2.1 Å)