8HAR

SAH-bound C-Methyltransferase Fur6 from Streptomyces sp. KO-3988

Summary for 8HAR

• Entry DOI: 10.2210/pdb8har/pdb
• Descriptor: Fur6, S-ADENOSYL-L-HOMOCYSTEINE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: furaquinocin, biosynthesis, biosynthetic protein
• Biological source: Streptomyces sp.
• Total number of polymer chains: 2
• Total formula weight: 77788.41

Authors

Noguchi, T.,Nagata, R.,Tomita, T.,Kuzuyama, T. (deposition date: 2022-10-26, release date: 2023-11-01, Last modification date: 2025-05-14)

Primary citation

Noguchi, T.,Zhao, F.,Moriwaki, Y.,Yamamoto, H.,Kudo, K.,Nagata, R.,Tomita, T.,Terada, T.,Shimizu, K.,Nishiyama, M.,Kuzuyama, T.
Biosynthesis of the tetrahydroxynaphthalene-derived meroterpenoid furaquinocin via reductive deamination and intramolecular hydroalkoxylation of an alkene.
Chem Sci, 2025

PubMed Abstract: Hybrid isoprenoid-polyketides, known as meroterpenoids, are a family of natural products that exhibit various bioactivities and are promising drug scaffolds. Despite the structural diversity of 1,3,6,8-tetrahydroxynaphthalene (THN)-derived meroterpenoids, such as furaquinocin, naphterpin, and furanonaphthoquinone, several biosynthetic genes for these compounds are conserved, suggesting a shared biosynthetic mechanism. However, the common biosynthetic mechanism and pathway-specific structural diversification mechanisms of these meroterpenoids are not yet fully understood. This study reveals the biosynthetic pathway for furaquinocin, demonstrating that it involves reductive deamination to form a key hydroquinone intermediate essential for subsequent reactions, including a unique cyclization step. We identified the mechanism of reductive deamination of the biosynthetic intermediate 8-amino-flaviolin through transient diazotization, leading to the formation of the hydroquinone intermediate 1,2,4,5,7-pentahydroxynaphthalene (PHN). Structural and computational studies confirmed that PHN is a key substrate for the subsequent methylation. We also showed that the hydroquinone intermediates are prerequisites for the subsequent pathway-specific reactions, including prenylation and novel intramolecular hydroalkoxylation of an alkene. This hydroalkoxylation reaction is notable in that a methyltransferase homolog catalyzes it in an -adenosylmethionine-independent manner. Our findings provide a new model for furaquinocin biosynthesis, offering insights into the biosynthetic strategies for THN-derived meroterpenoids.

PubMed: 40191119
DOI: 10.1039/d4sc08319a

Experimental method

X-RAY DIFFRACTION (2.12 Å)