Antitumor Anthraquinones from an Easter Island Sea Anemone: Animal or Bacterial Origin?

Abstract

The presence of two known anthraquinones, Lupinacidin A and Galvaquinone B, which have antitumor activity, has been identified in the sea anemone (Gyractis sesere) from Easter Island. So far, these anthraquinones have been characterized from terrestrial and marine Actinobacteria only. In order to identify the anthraquinones producer, we isolated Actinobacteria associated with the sea anemone and obtained representatives of seven actinobacterial genera. Studies of cultures of these bacteria by HPLC, NMR, and HRLCMS analyses showed that the producer of Lupinacidin A and Galvaquinone B indeed was one of the isolated Actinobacteria. The producer strain, SN26_14.1, was identified as a representative of the genus Verrucosispora. Genome analysis supported the biosynthetic potential to the production of these compounds by this strain. This study adds Verrucosispora as a new genus to the anthraquinone producers, in addition to well-known species of Streptomyces and Micromonospora. By a cultivation-based approach, the responsibility of symbionts of a marine invertebrate for the production of complex natural products found within the animal’s extracts could be demonstrated. This finding re-opens the debate about the producers of secondary metabolites in sea animals. Finally, it provides valuable information about the chemistry of bacteria harbored in the geographically-isolated and almost unstudied, Easter Island.

Genome-enabled discovery of anthraquinone biosynthesis in Senna tora

“…It is possible that other CHS-L genes might also participate in anthraquinone biosynthesis. Unlike in plants, anthraquinones are produced via type II PKS enzymes in bacteria such as Streptomyces 43 – 45 , Photorhabdus luminescens 46 , 47 , and Verrucosispora 48 . Thus, the biosynthetic route of anthraquinones is distinct in plants and other anthraquinone-producing organisms, illustrating a convergent metabolic evolution.…”

Biosynthesis of the Tricyclic Aromatic Type II Polyketide Rishirilide: New Potential Third Ring Oxygenation after Three Cyclization Steps

“…[ 2 ]. And recently the rishirilide derivative Lupinacidin A and Galvaquinone B have been isolated from the sea anemone Gyractis sesere [ 43 ]. These results indicate that intermediates of biosynthetic pathways to rishirilides can chemically be converted efficiently to galvaquinones.…”

Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives

“…They screened both metabolites for cytotoxic activity against Calu-3 and H2887 cancer cell lines and reported IC 50 values of 5.0 and 12.2 µM for 72 and 8.8 and 3.1 µM for 73, respectively. Recently, Sottorff and his team isolated both 72 and 73 from the sea anemone (Gyractis sesere) from Easter Island, but further confirmed the Actinobacteria of the genus Verrucosispora as the exact producer of those compounds [216].…”