8RQH

Crystal Structure of the flavoprotein monooxygenase TrlE from Streptomyces cyaneofuscatus Soc7

Summary for 8RQH

• Entry DOI: 10.2210/pdb8rqh/pdb
• Descriptor: Tropone 2-monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: tropolone, fad, oxidoreductase, decarboxylation, flavoprotein
• Biological source: Streptomyces cyaneofuscatus
• Total number of polymer chains: 2
• Total formula weight: 94308.34

Authors

Sowa, S.T.,Hoeing, L.S.,Jakob, R.P.,Maier, T.,Teufel, R. (deposition date: 2024-01-18, release date: 2024-05-15, Last modification date: 2024-06-05)

Primary citation

Hoing, L.,Sowa, S.T.,Toplak, M.,Reinhardt, J.K.,Jakob, R.,Maier, T.,Lill, M.A.,Teufel, R.
Biosynthesis of the bacterial antibiotic 3,7-dihydroxytropolone through enzymatic salvaging of catabolic shunt products.
Chem Sci, 15:7749-7756, 2024

PubMed Abstract: The non-benzenoid aromatic tropone ring is a structural motif of numerous microbial and plant natural products with potent bioactivities. In bacteria, tropone biosynthesis involves early steps of the widespread CoA-dependent phenylacetic acid (paa) catabolon, from which a shunt product is sequestered and surprisingly further utilized as a universal precursor for structurally and functionally diverse tropone derivatives such as tropodithietic acid or (hydroxy)tropolones. Here, we elucidate the biosynthesis of the antibiotic 3,7-dihydroxytropolone in Actinobacteria by pathway reconstitution using paa catabolic enzymes as well as dedicated downstream tailoring enzymes, including a thioesterase (TrlF) and two flavoprotein monooxygenases (TrlCD and TrlE). We furthermore mechanistically and structurally characterize the multifunctional key enzyme TrlE, which mediates an unanticipated -substitution involving a hydroxylation and subsequent decarboxylation of the CoA-freed side chain, followed by ring oxidation to afford tropolone. This study showcases a remarkably efficient strategy for 3,7-dihydroxytropolone biosynthesis and illuminates the functions of the involved biosynthetic enzymes.

PubMed: 38784727
DOI: 10.1039/d4sc01715c

Experimental method

X-RAY DIFFRACTION (2.5 Å)