Engineering deoxysugar biosynthetic pathways from antibiotic-producing microorganisms:: A tool to produce novel glycosylated bioactive compounds

被引:100
作者
Rodríguez, L
Aguirrezabalaga, I
Allende, N
Braña, AF
Méndez, C
Salas, JA [1 ]
机构
[1] Univ Oviedo, Dept Biol Func, E-33006 Oviedo, Spain
[2] Univ Oviedo, Inst Univ Oncol Principado Asturias, E-33006 Oviedo, Spain
来源
CHEMISTRY & BIOLOGY | 2002年 / 9卷 / 06期
关键词
D O I
10.1016/S1074-5521(02)00154-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A plasmid (pLN2) was generated in which genes involved in the biosynthesis of L-oleandrose in the oleandomycin producer Streptomyces antibioticus ATCC1 1891 were cloned. pLN2 was used to direct the biosynthesis of different deoxysugars; by exchanging and/or adding genes from other antibiotic biosynthetic clusters. Transfer of the synthesized deoxysugars to the tetracenomycin C aglycon, 8-demethyl-tetracenomycin C, through the use of the "sugar flexible" glycosyltransferase ElmGT, validated the system. Several pLN2 derivatives were constructed by replacement of the oleU 4-ketoreductase gene by different 4-ketoreductase genes. Some of them, such as EryBIV and UrdR, reduced the keto group of the 4-keto intermediates, generating L-olivosyl and D-olivosyl derivatives, respectively. The system was also used to generate an L-rhamnosyl derivative (through a two-gene deletion) and an L-rhodinosyl derivative (through a combination of a gene replacement and a gene addition).
引用
收藏
页码:721 / 729
页数:9
相关论文
共 47 条
[1]   Identification and expression of genes involved in biosynthesis of L-oleandrose and its intermediate L-olivose in the oleandomycin producer Streptomyces antibioticus [J].
Aguirrezabalaga, I ;
Olano, C ;
Allende, N ;
Rodriguez, L ;
Braña, AF ;
Méndez, C ;
Salas, JA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (05) :1266-1275
[2]  
ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
[3]   The mycinose-biosynthetic genes of Streptomyces fradiae producer of tylosin [J].
Bate, N ;
Cundliffe, E .
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY, 1999, 23 (02) :118-122
[4]   Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin [J].
Blanco, G ;
Patallo, EP ;
Braña, AF ;
Trefzer, A ;
Bechthold, A ;
Rohr, J ;
Méndez, C ;
Salas, JA .
CHEMISTRY & BIOLOGY, 2001, 8 (03) :253-263
[5]   Biosynthesis of desosamine: Construction of a new macrolide carrying a genetically designed sugar moiety [J].
Borisova, SA ;
Zhao, LS ;
Sherman, DH ;
Liu, HW .
ORGANIC LETTERS, 1999, 1 (01) :133-136
[6]  
BULLOCK WO, 1987, BIOTECHNIQUES, V5, P376
[7]   NOVEL GENETICALLY-ENGINEERED TETRACENOMYCINS [J].
DECKER, H ;
HAAG, S ;
UDVARNOKI, G ;
ROHR, J .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1995, 34 (10) :1107-1110
[8]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395
[9]   Interspecies complementation in Saccharopolyspora erythraea:: elucidation of the function of oleP1, oleG1 and oleG2 from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus and generation of new erythromycin derivatives [J].
Doumith, M ;
Legrand, R ;
Lang, C ;
Salas, JA ;
Raynal, MC .
MOLECULAR MICROBIOLOGY, 1999, 34 (05) :1039-1048
[10]  
Fernández E, 1998, J BACTERIOL, V180, P4929