6ZYK

Non-heme monooxygenase, ThoJ-Ni complex

Summary for 6ZYK

• Entry DOI: 10.2210/pdb6zyk/pdb
• Descriptor: Monooxygenase, NICKEL (II) ION, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: non-heme monooxygenase, metal binding protein
• Biological source: Streptomyces malaysiense
• Total number of polymer chains: 1
• Total formula weight: 33787.15

Authors

Koehnke, J.,Sikandar, A. (deposition date: 2020-08-02, release date: 2020-10-14, Last modification date: 2024-01-31)

Primary citation

Sikandar, A.,Lopatniuk, M.,Luzhetskyy, A.,Koehnke, J.
Non-Heme Monooxygenase ThoJ Catalyzes Thioholgamide beta-Hydroxylation.
Acs Chem.Biol., 15:2815-2819, 2020

PubMed Abstract: Thioviridamide-like compounds, including thioholgamides, are ribosomally synthesized and post-translationally modified peptide natural products with potent anticancer cell activity and an unprecedented structure. Very little is known about their biosynthesis, and we were intrigued by the β-hydroxy-N1, N3-dimethylhistidinium moiety found in these compounds. Here we report the construction of a heterologous host capable of producing thioholgamide with a 15-fold increased yield compared to the wild-type strain. A knockout of , encoding a predicted nonheme monooxygenase, shows that ThoJ is essential for thioholgamide β-hydroxylation. The crystal structure of ThoJ exhibits a typical mono/dioxygenase fold with conserved key active-site residues. Yet, ThoJ possesses a very large substrate binding pocket that appears suitable to receive a cyclic thioholgamide intermediate for hydroxylation. The improved production of the heterologous host will enable the dissection of the individual biosynthetic steps involved in biosynthesis of this exciting RiPP family.

PubMed: 32965102
DOI: 10.1021/acschembio.0c00637

Experimental method

X-RAY DIFFRACTION (2.55 Å)