Erythrolic acids A-E, Meroterpenoids from a Marine-Derived Erythrobacter sp.

Department of Biochemistry, Division of Chemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
The Journal of Organic Chemistry (Impact Factor: 4.72). 03/2012; 77(7):3401-7. DOI: 10.1021/jo300197z
Source: PubMed


Erythrolic acids A-E (1-5) are five unusual meroterpenoids isolated from the bacterium Erythrobacter sp. derived from a marine sediment sample collected in Galveston, TX. The structures were elucidated by means of detailed spectroscopic analysis and chemical derivatization. The erythrolic acids contain a 4-hydroxybenzoic acid appended with a modified terpene side chain. The side-chain modifications include oxidation of a terminal methyl substituent and in the case of 1-4 addition of a two-carbon unit to give terpene side chains of unusual length: C22 for 1 and 2, C17 for 3, and C12 for 4. The relative and absolute configurations of the meroterpenoids were determined by coupling constant, NOE, and Mosher's analysis. In vitro cytotoxicity toward a number of nonsmall cell lung cancer (NSCLC) cell lines revealed only modest activity for erythrolic acid D (4) (2.5 μM against HCC44). The discovery of these unusual diterpenes, along with the previously reported erythrazoles, demonstrates the natural product potential of a previously unstudied group of bacteria for drug discovery. The unusual nature of the terpene side chain, we believe, involves an oxidation of a terminal methyl group to a carboxylic acid and subsequent Claisen condensation with acetyl-CoA.

Download full-text


Available from: Ana Paula Espindola, Mar 17, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biocatalysis has become an important method in the pharmaceutical industry for the incorporation of new functionality in small molecules. Currently this method is limited in the types of reactions that can be carried out and no strategy exists to systematically screen for new biocatalyzed reactions. This study involves the development of a medium throughput screen to identify and optimize new reactions using a series of marine-derived bacterial cell lines, which were screened against several (13)C labeled organic substrates. The reactions were analyzed using (13)C NMR as the primary screening tool. We describe the discovery of a bacterial catalyzed indole oxidation reaction in which complete conversion of (13)C labeled N-methyl indole to 3-hydroxyindole was observed. In addition, the sensitivity of this reaction to dO(2) levels can be exploited to oxidize to either 3-hydroxyindole or 2-oxoindole. This new platform sets up an important tool for the discovery of new organic transformations using an extensive library of marine bacteria.
    No preview · Article · Jul 2012 · Journal of the American Chemical Society
  • [Show abstract] [Hide abstract]
    ABSTRACT: Four new anthraquinone analogues including galvaquinones A-C (1-3) and an isolation artifact, 5,8-dihydroxy-2,2,4-trimethyl-6-(3-methylbutyl)anthra[9,1-de][1,3]oxazin-7(2H)-one (4), were isolated from a marine-derived Streptomyces spinoverrucosus based on activity in an image-based assay to identify epigenetic modifying compounds. The structures of 1-4 were elucidated by comprehensive NMR and MS spectroscopic analysis. Galvaquinone B (2) was found to show epigenetic modulatory activity at 1.0 μM and exhibited moderate cytotoxicity against non-small-cell lung cancer (NSCLC) cell lines Calu-3 and H2887.
    No preview · Article · Oct 2012 · Journal of Natural Products
  • [Show abstract] [Hide abstract]
    ABSTRACT: The microbial drug research started from the 20th century has become the foundation of modern drugs. Nowadays, almost 10% of all presently known compounds with bioactivities are of microbial origin. In the past decade, natural products from marine microorganisms that were regarded as a very potential resource for the drug discovery have gained great attention. This paper introduces the sources, structures and bioactivities of 895 new compounds from marine bacteria, actinomycetes and fungi reported between January 2010 and February 2013.
    No preview · Article · Jun 2013 · Chinese Journal of Organic Chemistry
Show more