Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1 -: I.: Fermentation, isolation and biological activity

被引:50
作者
Pacey, MS [1 ]
Dirlam, JP
Geldart, RW
Leadlay, PF
McArthur, HAI
McCormick, EL
Monday, RA
O'Connell, TN
Staunton, J
Winchester, TJ
机构
[1] Pfizer Cent Res, Anim Hlth Cent Res, Sandwich, Kent, England
[2] Pfizer Inc, Pfizer Cent Res, Anim Hlth Cent Res, Groton, CT 06340 USA
[3] Pfizer Bioproc R&D, Groton, CT USA
[4] Univ Cambridge, Cambridge Ctr Mol Recognit, Cambridge, England
[5] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England
关键词
D O I
10.7164/antibiotics.51.1029
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338. Both strains incorporated exogenously supplied fatty acids to produce novel, biologically active, C-13 substituted erythromycins.
引用
收藏
页码:1029 / 1034
页数:6
相关论文
共 15 条
[1]  
[Anonymous], 1993, METHODS DILUTION ANT
[2]   Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase [J].
Aparicio, JF ;
Molnar, I ;
Schwecke, T ;
Konig, A ;
Haydock, SF ;
Khaw, LE ;
Staunton, J ;
Leadlay, PF .
GENE, 1996, 169 (01) :9-16
[3]   IVERMECTIN - A REVIEW OF EFFICACY AND SAFETY [J].
CAMPBELL, WC ;
BENZ, GW .
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 1984, 7 (01) :1-16
[4]   AN UNUSUALLY LARGE MULTIFUNCTIONAL POLYPEPTIDE IN THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE OF SACCHAROPOLYSPORA-ERYTHRAEA [J].
CORTES, J ;
HAYDOCK, SF ;
ROBERTS, GA ;
BEVITT, DJ ;
LEADLAY, PF .
NATURE, 1990, 348 (6297) :176-178
[5]   ERYTHROMYCIN SERIES .11. RING EXPANSION F ERYTHROMYCIN-A OXIME BY THE BECKMANN REARRANGEMENT [J].
DJOKIC, S ;
KOBREHEL, G ;
LAZAREVSKI, G ;
LOPOTAR, N ;
TAMBURASEV, Z ;
KAMENAR, B ;
NAGL, A ;
VICKOVIC, I .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1986, (11) :1881-1890
[6]   MODULAR ORGANIZATION OF GENES REQUIRED FOR COMPLEX POLYKETIDE BIOSYNTHESIS [J].
DONADIO, S ;
STAVER, MJ ;
MCALPINE, JB ;
SWANSON, SJ ;
KATZ, L .
SCIENCE, 1991, 252 (5006) :675-679
[7]   NOVEL AVERMECTINS PRODUCED BY MUTATIONAL BIOSYNTHESIS [J].
DUTTON, CJ ;
GIBSON, SP ;
GOUDIE, AC ;
HOLDOM, KS ;
PACEY, MS ;
RUDDOCK, JC ;
BULOCK, JD ;
RICHARDS, MK .
JOURNAL OF ANTIBIOTICS, 1991, 44 (03) :357-365
[8]   ERYTHROMYCIN .1. PROPERTIES AND DEGRADATION STUDIES [J].
FLYNN, EH ;
SIGAL, MV ;
WILEY, PF ;
GERZON, K .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1954, 76 (12) :3121-3131
[9]   CORRELATION OF THE AVERMECTIN POLYKETIDE SYNTHASE GENES TO THE AVERMECTIN STRUCTURE - IMPLICATIONS FOR DESIGNING NOVEL AVERMECTINS [J].
MACNEIL, DJ ;
OCCI, JL ;
GEWAIN, KM ;
MACNEIL, T .
RECOMBINANT DNA TECHNOLOGY II, 1994, 721 :123-132
[10]  
MCGUIRE JM, 1961, ANTIBIOT CHEMOTHER, V11, P320