Undescribed benzophenone and xanthones from cave-derived Streptomyces sp. CB09001

Abstract

A new benzophenone huanglongmycin (HLM) D (1) and two new monomeric xanthones huanglongmycin E (2) and F (3), together with four known aromatic polyketides aloesaponarin II (4) and the previously isolated huanglongmycin A-C (5-7) obtained from cave-derived Streptomyces sp. CB09001. The structures of 1-3 were established based on 1D, 2D NMR and HRMS data. Compounds 1-7 may be biosynthesized by a type II huanglongmycin polyketide synthase based on gene inactivation of hlmG encoding KSɑ in hlm gene cluster and their plausible biosynthetic mechanism was proposed.

Discovery of a DNA Topoisomerase I Inhibitor Huanglongmycin N and Its Congeners from Streptomyces sp. CB09001

“…The stereochemistry of C-2 in 10 was determined as (R) by a comparison between the optical rotations of (R)-wailupemycin K (16) ([α] D 25 = +48.0, c 0.1, MeOH) 12 and 10 ([α] D 25 = +26.4, c 0.25, MeOH). HLM K (11) was obtained as a white solid with a molecular formula of C 14 H 10 O 4 based on its HRESIMS ion peak at m/z 245.0812 ([M + H] + , calcd 245.0814). The 1D and 2D NMR data of 11 were similar to those obtained for 10 (Table 3).…”

“…CB09001::ΔhlmG led to the abolishment of 1−17 production, suggesting that the Hlm type II PKS is responsible for their biosynthesis (Figures 5 and S7). 10,11 Compounds 7 and 8 may arrive from the incomplete and nonenzymatic aromatization of cyclic intermediates, similar to julichrome monomers (Figure 5). 16 The isolation of shunt metabolites 9, 15, and 16 suggests the leaking of polyketide intermediates by Hlm PKS under specific fermentation conditions before the C7−C14 first-ring cyclization, similar to the previously isolated 2 and 3.…”

“…10 In addition, the biosynthetic pathway for 1 and congeners 2−6 and 17 by aromatic polyketide synthase (PKS) has been identified and preliminarily characterized. 10,11 In this study, we describe the isolation and structure elucidation of two new anthraquinones 13 and 14 as well as six undescribed shunt polyketides 7−12 from this strain, which were derived from the same biosynthetic pathway. Among them, HLM N (14) exhibited 0.07−0.51 μM cytotoxicity against the tested cancer cells and inhibited top1 activity with an EC 50 of ∼14 μM.…”