Mccrearamycins A–D, Geldanamycin‐Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe

Abstract

Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.

Neoansamycins from Streptomyces sp. LZ35

“…17 Their highly diversied structures mostly resulted from diverse post-PKS modications. 12,18 In particular, post-PKS modications are critical in determining their bioactivities. 3,19 The structures of neoansamycins D-I mirror diverse and interesting post-PKS modications.…”

Insecticidal Endostemonines A–J Produced by Endophytic Streptomyces from Stemona sessilifolia

“…Subfraction J2 (84 mg) was further purified by prep-HPLC Table 1. 13 13 C and 1 H NMR data, see Tables 1 and 2 Endostemonine B (2). Yellow-brown oily substance; [α] D 20 −36.9 (c 0.1, MeOH); 13 C and 1 H NMR data, see Tables 1 and 2 Endostemonine C (3).…”

“…Yellow-brown oily substance; [α] D 20 −35.5 (c 0.2, MeOH); 13 C and 1 H NMR data, see Tables 1 and 2 Endostemonine F (6). Yellow-brown oily substance; [α] D 20 −38.0 (c 0.2, MeOH); 13 C and 1 H NMR data, see Tables 1 and 2 Endostemonine G (7). Yellow-brown oily substance; [α] D 20 −24.3 (c 0.6, MeOH); 13 C and 1 H NMR data, see Tables 1 and 2 Endostemonine H (8).…”

hcapca: Automated Hierarchical Clustering and Principal Component Analysis of Large Metabolomic Datasets in R

“…While the tools used to identify strains with diverse chemistry are immensely important, the chemical diversity is also dependent on the environment where samples originate. New and diverse chemistry can be accessed by exploring non-traditional environmental niches such as caves and insect symbionts, making new sources for lead compounds available [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Although this increases the likelihood of finding new chemical entities, it is still difficult to identify these elusive molecules because a majority of the molecules produced are often shared, even across different genera.…”