Addition of cerulenin (0.25-1.0 mM) to cultures of Acinomadura verrucosospora before the onset of esperamicin synthesis inhibited the production of esperamicin A1 by the microorganism. This result indicates that esperamicin A1 is biosynthesized in part by the polyketide pathway. Addition of cerulenin to the cultures during the active production phase led to a net decrease in esperamicin A1 production. The 14C-acetate labeling pattern of esperamicin A1 in the cultures with or without addition of cerulenin at the active production phase also demonstrated the instability of esperamicin A1 in the fermentation. This suggests that esperamicin A1 is unstable and degradation occurs during the active production phase. Addition of the neutral resin Diaion HP-20 (1%) to the fermentation enhanced the production of esperamicin A1 by 53%.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF01569908DOI Listing

Publication Analysis

Top Keywords

production esperamicin
12
addition cerulenin
12
active production
12
production phase
12
esperamicin
9
production
6
cerulenin
4
cerulenin production
4
esperamicin actinomadura
4
actinomadura verrucosospora
4

Similar Publications

Actinobacteria, the bacterial phylum most renowned for natural product discovery, has been established as a valuable source for drug discovery and biotechnology but is underrepresented within accessible genome and strain collections. Herein, we introduce the Natural Products Discovery Center (NPDC), featuring 122,449 strains assembled over eight decades, the genomes of the first 8490 NPDC strains (7142 Actinobacteria), and the online NPDC Portal making both strains and genomes publicly available. A comparative survey of RefSeq and NPDC Actinobacteria highlights the taxonomic and biosynthetic diversity within the NPDC collection, including three new genera, hundreds of new species, and ~7000 new gene cluster families.

View Article and Find Full Text PDF

A variety of fragmentations and rearrangements can follow Bergman cyclization in enediynes equipped with acetal rings mimicking the carbohydrate moiety of natural enediyne antibiotics of the esperamicine and calchiamicine families. In the first step of all these processes, intramolecular H-atom abstraction efficiently intercepts the p-benzyne product of the Bergman cyclization through a six-membered TS and transforms the p-benzyne into a new more stable radical. Depending on the substitution pattern and reaction conditions, this radical follows four alternative paths: (a) abstraction of an external hydrogen atom, (b) O-neophyl rearrangement which transposes O- and C-atoms of the substituent, (c) fragmentation of the O-C bond in the acetal ring, or (d) fragmentation with elimination of the appended acetal moiety as a whole.

View Article and Find Full Text PDF

Disulfide and multisulfide antitumor agents and their modes of action.

Arch Pharm Res

March 2009

College of Pharmacy, Duksung Women's University, Seoul, 132-714, Korea.

A variety of natural products that contain disulfide or multisulfide bonds were found to display potent biological activities, including antitumor activities. At the center of these biological activities are disulfide or multisulfide moieties. The importance of disulfide or multisulfide groups in the areas of chemistry, biology, and pharmacology has been well recognized.

View Article and Find Full Text PDF

Incorporation of enediynes into anticancer drugs remains an intriguing yet elusive strategy for the design of therapeutically active agents. Density functional theory was used to locate reactants, products, and transition states along the Bergman cyclization pathways connecting enediynes to reactive para-biradicals. Sum method correction to low-level calculations confirmed B3LYP/6-31G(d,p) as the method of choice in investigating enediynes.

View Article and Find Full Text PDF

Mechanistic analyses of site-specific degradation in DNA-RNA hybrids by prototypic DNA cleavers.

Nucleic Acids Res

May 1997

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.

Bleomycin (BLM) binding and chemistry are apparently sensitive to differences in nucleic acid conformation and could conceivably be developed as a probe for sequence-dependent elements of conformation. We report on the development of a new methodology to synthesize heterogeneous DNA-RNA hybrids of defined sequence and present the results of our comparative studies on the cleavage of DNA and DNA-RNA hybrids by four drugs: BLM, neocarzinostatin and esperamicins A1 and C. In the case of BLM with duplex DNA, purine-pyrimidine steps such as GT and GC, are consistently hit, as previously observed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!