Naphthoquinone-like Polyketide Isolated from Streptomyces sp. RI-77 and Its Predicted Biosynthetic Pathway

Abstract

A novel naphthoquinone-like polyketide, JBIR-85 (1), with a unique skeleton and antioxidative activity was isolated from a culture of Streptomyces sp. RI-77. The planar structure of 1 was established on the basis of extensive NMR and MS analyses. The structure of 1 including the absolute configuration was established via X-ray crystallographic analysis. Since 1 exhibits a unique skeleton, we performed feeding experiments to reconfirm the structure and predict the biosynthetic pathway.

Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization

“…To understand the role of the ANS pathway in natural product biosynthesis, we focused on the biosynthetic gene cluster containing creE and creD homologs ( avaE and avaD ) in Streptomyces sp. RI‐77 (Figure 1A, Table 1), which produces two different families of aromatic polyketides (JBIR‐85 and isofuranonaphthoquinones [JBIR‐76, ‐77]) biosynthesized by type II polyketide synthases (PKSs) [24–26] . We named this cluster ava (avenalumic acid) because this cluster was later shown to be responsible for the biosynthesis of avenalumic acid (see below).…”

“…RI-77 (Figure 1A, Table 1), which produces two different families of aromatic polyketides (JBIR-85 and isofuranonaphthoquinones [JBIR-76, -77]) biosynthesized by type II polyketide synthases (PKSs). [24][25][26] We named this cluster ava (avenalumic acid) because this cluster was later shown to be responsible for the biosynthesis of avenalumic acid (see below). The ava gene cluster encodes a set of 3-amino-4-hydroxybenzoic acid (3,4-AHBA, 1) synthase homologs (AvaI and AvaH), putative type II PKSs (AvaA2-A5 and AvaA8), two putative acyl- CoA ligases (AvaA1 and AvaA6), two putative transporters, and one hypothetical protein.…”

Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications

“…1 b), have been extensively studied as anticancer and antibiotic drugs. Interestingly, we also noticed a group of polyketides with all-carbon quaternary centers within the core anthracenols or anthraquinones, such as the newly isolated A-74528 ( 3 ) 5 , 6 and JBIR-85 ( 4 ) 7 , as well as the antibiotics pleurotin ( 5 ) 8 – 13 and oncocalyxone B ( 6 ) 14 , 15 . The additional quaternary carbons contribute to the diversity of these challenging chemical structures.…”

Hot off the press

“…RI-77 with a novel skeleton. 15 Tenuipyrone 20, a metabolite of the fungus Isaria tenuipes, also have a novel polyketide skeleton. 16 The authors propose that tenuipyrone 20 is formed from two polyketide chains.…”