The Electrospray Ionization - Mass Spectra of Erythromycin A Obtained from a Marine Streptomyces sp. Mutant

In our ongoing search for production improvements of bioactive secondary metabolites from marine Streptomyces through the induction of mutations using UV light, out of 145 isolates, mutant 10/14 was able to produce potent antibacterial metabolites other than the parent strain as established by chromatographic analysis. Up-scaling fermentation of mutant 10/14, followed by working up and isolation delivered five metabolites, phenazine, 1-acetyl-β -carboline, perlolyrin and erythromycin A, along with an oily substance. The latter two compounds were responsible for the antibacterial activity of the strain. In this article, we discuss with the mutation of the marine Streptomyces sp. AH2, bioactivity evaluation, fermentation and isolation of the microbial metabolites. Moreover, we study to first time in detail the 1D and 2D NMR and ESI MS data including ESI MS2 and MS3 patterns combined with HRESI MS of erythromycin A.

[1]  G. Beznoussenko,et al.  Intra-Golgi transport , 2008 .

[2]  K. Rainsford Influenza (“Bird Flu”), inflammation and anti-inflammatory/analgesic drugs , 2006, InflammoPharmacology.

[3]  A. El-Bondkly Construction of superior Streptomyces noursei fusants for nystatin and antibacterial antibiotics production , 2006 .

[4]  M. Mahmoud Bioactive Secondary Metabolites from Marine and Terrestrial Bacteria: Isoquinolinequinones, Bacterial Compounds with a Novel Pharmacophor , 2005 .

[5]  H. Laatsch Marine Bacterial Metabolites , 2005 .

[6]  H. Hirai,et al.  Daunomycin-arachidonic acid complex as a potential new antitumor agent , 2004, Cancer Chemotherapy and Pharmacology.

[7]  S. Bejar,et al.  Isolation, purification and partial characterization of antibacterial activities produced by a newly isolated Streptomyces sp. US24 strain. , 2003, Research in microbiology.

[8]  S. Hwang,et al.  Enhancement of clavulanic acid production in Streptomyces clavuligerus with ornithine feeding , 2003 .

[9]  A. Demain,et al.  Mutagenesis of the rapamycin producer Streptomyces hygroscopicus FC904. , 2001, The Journal of antibiotics.

[10]  S. Jensen,et al.  Applications of Gene Replacement Technology toStreptomyces clavuligerus Strain Development for Clavulanic Acid Production , 2001, Applied and Environmental Microbiology.

[11]  B. Rawlings Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis). , 2001, Natural product reports.

[12]  S. H. Lee,et al.  Improvement of tylosin fermentation by mutation and medium optimization , 1999, Letters in applied microbiology.

[13]  K. Resing,et al.  Alkylation of DNA by the anthracycline, antitumor drugs adriamycin and daunomycin. , 1996, Journal of medicinal chemistry.

[14]  S. Munro,et al.  Intra-Golgi Transport Inhibition by Megalomicin (*) , 1996, The Journal of Biological Chemistry.

[15]  R. Lal,et al.  Rifamycins: strain improvement program. , 1995, Critical reviews in microbiology.

[16]  T. Adachi,et al.  Hydroxylation and N-demethylation of clarithromycin (6-O-methylerythromycin A) by Mucor circinelloides. , 1989, The Journal of antibiotics.

[17]  J. Hoogmartens,et al.  Identification of novel erythromycin derivatives in mother liquor concentrates of Streptomyces erythraeus. , 1987, The Journal of antibiotics.

[18]  E. Roets,et al.  Isolation of erythromycins and related substances from fermentation residues of streptomyces erythreus by high-performance liquid chromatography on silica gel , 1985 .

[19]  R. Rodrigo,et al.  A CONVERGENT SYNTHESIS OF (±)DAUNOMYCINONE , 1984 .

[20]  R. Spagnoli,et al.  Erythronolide A glycosidation to erythromycin A by a blocked mutant of Streptomyces erythraeus. , 1983, The Journal of antibiotics.

[21]  J. R. Martin,et al.  A new naturally occurring erythromycin: erythromycin F. , 1982, The Journal of antibiotics.

[22]  G. Lukács,et al.  Natural abundance 13C13C coupling constants observed via double quantum coherence. The two-dimensional ‘inadequate’ experiment for 13C NMR spectral analysis of erythronolide - B , 1982 .

[23]  D. Henry,et al.  Synthetic approaches to adriamycin. 2. Degradation of daunorubicin to a nonasymmetric tetracyclic ketone and refunctionalization of the A ring to adriamycin. , 1977, The Journal of organic chemistry.

[24]  J. Wieczorek,et al.  Antibiotics produced by Streptomyces olivaceus 142. I. Characterization of the FPG mutant and conditions of production of antibiotic WR 142-FPG. , 1976, Archivum immunologiae et therapiae experimentalis.

[25]  R. L. Girolami,et al.  Studies on the biosynthesis of the erythromycins. I. Isolation and structure of an intermediate glycoside, 3-alpha-L-mycarosylerythronolide B. , 1966, Biochemistry.