Polypeptides involved in the biosynthesis of spiramycins, nucleotide sequences coding these polypeptides and their uses

摘要

Polynucleotide (I) that encodes a polypeptide involved in biosynthesis of spiramycin (A) is any of 47 sequences (B) given in the specification, variants (B') of (B), or equivalents of (B) and (B') within the degeneracy of the genetic code. Independent claims are also included for the following: (1) polynucleotides (Ia) that hybridize to (I) under stringent conditions; (2) polynucleotides (Ib) that are at least 70% identical with at least 10 consecutive nucleotides (nt) of (I); (3) polypeptide (II) expressed by (I), (Ia) or (Ib); (4) polypeptides (IIa) involved in synthesis of (A) that have any of 61 sequences (C), reproduced, derivatives (C') of (C) having one or more substitutions, insertions or deletions of amino acids (aa) in (C), and variants of (C) and (C'); (5) polypeptide (IIb) at least 70% identical with at least 10 consecutive aa of (IIa); (6) recombinant DNA (Ic) that contains at least one (I), (Ia) or (Ib); (7) expression vector containing at least one sequence encoding (IIa) or (IIb); (8) expression system comprising vector and host cells able to produce (IIa) or (IIb); (9) host cell containing at least one (I), (Ia), (Ib), (Ic) or the vector of (7); (10) method for producing (IIa) or (IIb); (11) microorganisms (X) blocked in a stage in the biosynthetic pathway of at least one macrolide (M); (12) the Streptomyces ambofaciensstrains CNCM I-2909 or 2911-2917, also SPM510; (13) method for preparing intermediates (MI) in biosynthesis of (M); (14) method for preparing a macrolide derivative (MD) by modification of MI; (15) microorganism (Y) that produces spiramycin I (AI) but not spiramycins II and III; (16) the Streptomyces ambofaciensstrain CNCM I-2910; (17) method for preparing (AI); (18) mutant microorganism (Z) that produces an (M) and has a genetic modification in at least one (I), (Ia) or (Ib) and/or overexpresses such sequences; (19) method for producing (M) by culturing (Z); (20) polynucleotide (Id) that is the complement of (I), (Ia) or (Ib); (21) microorganism (Z1) that produces at least one spiramycin and overexpresses a specific gene (Ie) or its degenerate equivalents; (22) strain S. ambofaciensOSC2/pSPM75(1 or 2), deposited as CNCM I-3101; (23) recombinant DNA (If) amplified from the S. ambofaciensplasmid pSPM36, or its fragments of at least 10 nucleotides; (24) vector containing (If); and (25) method for producing a polypeptide, using the vector of (24). ACTIVITY : Antibacterial; Immunosuppressive; Antirheumatic; Antiarthritic: Anthelmintic; Insecticide. No details of tests for these activities are given. MECHANISM OF ACTION : None given.