Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for...
Patent
1995-05-10
1999-04-06
Hendricks, Keith D.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
435 41, 435189, 43525233, 4353201, 435 691, 530350, 536 231, 536 232, 536 237, C12N 900, C12N 120, C07H 2104
Patent
active
058916954
DESCRIPTION:
BRIEF SUMMARY
This is U.S. national stage application of PCT/FR93/00923, filed Sep. 25, 1993 (WO/08014).
FIELD OF THE INVENTION
The present invention relates to novel polypeptides involved in the biosynthesis of streptogramins, and also comprises the isolation and identification of genes for the biosynthesis of the A and B components of streptogramins, the expression of these genes with the object of increasing the levels of production and their use for the construction of blocked mutants capable of leading to the synthesis of novel antibiotics or to derived forms of streptogramins.
BACKGROUND OF THE INVENTION
Streptogramins form a homogeneous group of antibiotics, consisting of a combination of two types of molecules which are chemically different; on the one hand polyunsaturated macrolactones (A-group components, two examples of structures of which are presented in FIG. 1), and on the other hand depsipeptides (B-group components, three examples of the structure of which are presented in FIG. 2). This group comprises many antibiotics (see Table 1 and FIG. 3), which are known by different names in accordance with their origin, including pristinamycins, mikamycins and virginiamycins (for a review, see Cocito 1979, 1983).
The A and B components have a synergistic antibacterial activity which can reach 100 times that of the separate components and which, in contrast to that of each component, is bactericidal (Cocito 1979). This activity is more especially effective against Gram-positive bacteria such as staphylococci and streptococci (Cocito 1979, Videau 1982). The A and B components inhibit protein synthesis by binding to the 50S subunit of the ribosome (Cocito 1979; for a review, see Di Giambattista et al. 1989).
Streptogramins are chiefly produced by actinomycetes, including many streptomycetes, presented in Table 1. In addition, streptogramins are also synthesized by eukaryotes such as Micromonospora which synthesizes vernamycins. Actinomycetes constitute a very important group of microorganisms on account of the large amount of secondary metabolites they produce, including many antibiotics (beta-lactams, tetracyclines, macrolides, aminoglycosides, polyacetates and the like), herbicides, anticancer agents, antifungal agents, immunomodulators and enzyme inhibitors. Many biosynthesis pathways relating to antibiotics belonging to miscellaneous classes as well as other secondary metabolites such as pigments (for a review, Chater 1990) have already been studied at the present time in actinomycetes. An important aspect of this group of bacteria is that the genes involved in the same biosynthesis pathway, structural genes and also resistance gene(s) and regulatory gene(s), are grouped together physically on the chromosome, constituting clusters which can reach more than 100 kb (Hopwood et al. 1986a, Hopwood et al. 1986b, Hallam et al. 1988, Anzai et al. 1987, Ohnuki et al. 1985). To date, no example has been found to contradict this observation. Such a structural organization is of great interest in the development of strategies for cloning biosynthesis genes. In effect, it is possible, starting from a single gene previously cloned by various techniques, a biosynthesis, resistance or regulatory gene, to walk along the chromosome and thus to isolate the set of genes of the biosynthesis cluster.
Our knowledge of the biosynthesis pathways of each of the components of streptogramins is still very incomplete, but the origin of the different parts of each molecule has been identified by radioactive labelling (Kingston et al. 1983). Thus, the A-type components are made up of two regions originating from the condensation of acetates and several amino acids such as serine and glycine, for example. As regards the B-type components, studies have shown that all the amino acids present in the peptide chain are derived from natural amino acids (Hook and Vining 1973). However, no polypeptide involved in these pathways has, to date, been purified in sufficient amounts to permit its molecular characterization, and no biosynthesis gene h
REFERENCES:
patent: 5252474 (1993-10-01), Gewain et al.
patent: 5591614 (1997-01-01), Blanche et al.
Spyrou et al. "Characterization of the flavin reductase gene (fre) of Escherichia coli and construction of a plasmid of over production of the enzyme" J. Bacteriol. 173, 3673-3679, Jun. 1991.
Francis et al. "Biosynthesis of chloramphenicol in streptomyces species 3022a: the nature of arylamine synthetase system" Can. J. Microbiol. 25, 1408-1515, 1979.
Biotechnology; vol. 8; Feb. 1990; NY, US; pp. 115-121, Chater et al.; "The improving prospects for yield increase by genetic engineering . . . ".
Gene; vol. 74; 1988; Amsterdam, NL; pp. 305-320; Hallam et al.; "Nucleotide sequence transcription and deduced function of a gene . . . ".
Chemical Abstracts; vol. 115; No. 23; Dec. 1991; abstract No. 251978n; Funane, Kazumi et al.; "Isolation and properties of IM factor . . . ".
Drugs and the Pharmaceutical Sciences; vol. 22; 1984; pp. 695-720; A. M. Biot; "Virginiamycin: properties, biosynthesis and fermentation".
Biotechnology Letters; vol. 14; No. 11; Nov. 1992; pp. 1065-1070; Paquet et al; "Induction of pristinamycins production in Streptomyces".
Database WPI; Sec. CH; Week 8420; Apr. 1984; Derwent Publ.; London GB; Class B02, AN 84-123313; "Selective production of neoviridogrisein . . . ", Abstract.
Folia Microbiologica; vol. 35; No. 6; 1990; Prague; p. 494; "Abstract" M. Blumauerova; Physiological and genetic aspects of Virginiamycin . . .
Biotechnology and Bioindustry; vol. 2; 1988; pp. 20-21; V. Prykrylova "Strain development in Streptomyces virginiae, a producer of . . . ".
Blanc Veronique
Blanche Francis
Crouzet Joel
De Crecy-Lagard Valerie
Debussche Laurent
Hendricks Keith D.
Nashed Nashaat T.
Rhone-Poulenc Rorer S.A.
LandOfFree
Polypeptides involved in the biosynthesis of streptogramins, nuc does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polypeptides involved in the biosynthesis of streptogramins, nuc, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polypeptides involved in the biosynthesis of streptogramins, nuc will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1370484