8har

Publication Abstract from PubMed

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 S-adenosylmethionine-independent manner. Our findings provide a new model for furaquinocin biosynthesis, offering insights into the biosynthetic strategies for THN-derived meroterpenoids.

Biosynthesis of the tetrahydroxynaphthalene-derived meroterpenoid furaquinocin via reductive deamination and intramolecular hydroalkoxylation of an alkene.,Noguchi T, Zhao F, Moriwaki Y, Yamamoto H, Kudo K, Nagata R, Tomita T, Terada T, Shimizu K, Nishiyama M, Kuzuyama T Chem Sci. 2025 Mar 31;16(18):7912-7920. doi: 10.1039/d4sc08319a. eCollection 2025 , May 7. PMID:40191119^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.