THE SUBSTRATE-SPECIFICITY OF DEACETOXYCEPHALOSPORIN-C SYNTHASE (EXPANDASE) OF STREPTOMYCES-CLAVULIGERUS IS EXTREMELY NARROW

被引：19
作者：
MAEDA, K
LUENGO, JM
FERRERO, O
WOLFE, S
LEBEDEV, MY
FANG, A
DEMAIN, AL
机构：
[1] MIT,DEPT BIOL,FERMENTAT MICROBIOL LAB,CAMBRIDGE,MA 02139
[2] UNIV LEON,DEPT BIOQUIM & BIOL MOLEC,LEON,SPAIN
[3] SIMON FRASER UNIV,DEPT CHEM,BURNABY,BC V5A 1S6,CANADA
来源：
ENZYME AND MICROBIAL TECHNOLOGY | 1995年 / 17卷 / 03期
关键词：
ANTIBIOTICS; CEPHALOSPORINS; EXPANDASE; DEACETOXYCEPHALOSPORIN C SYNTHASE; STREPTOMYCES CLAVULIGERUS; SUBSTRATE SPECIFICITY; SECONDARY METABOLISM;
D O I：
10.1016/0141-0229(94)00001-8
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：
Cell-free extracts of Streptomyces clavuligerus contain the enzyme deacetoxycephalosporin C synthase (''expandase''), which catalyzes the oxidative ring expansion of the natural substrate delta-o-alpha-aminoadipyl-6-APA (penicillin N) into the primary cephalosporin, deacetoxycephalosporin C in the presence of magnesium ions, ferrous ions, ascorbate, and a-ketoglutarate. Eighteen unnatural side chain analogues of penicillin N were exposed to these reaction conditions. Only D-carboxymethylcysteinyl-6-APA was found to undergo ring expansion. Of special interest is the observation that adipyl-6-APA and m-carboxyphenylacetyl-6-APA were not expanded.
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页码：231 / 234
页数：4
相关论文
共 20 条
[1]   ENZYMATIC-SYNTHESIS OF PENICILLINS [J].
ALONSO, MJ ;
BERMEJO, F ;
REGLERO, A ;
FERNANDEZCANON, JM ;
DEBUITRAGO, GG ;
LUENGO, JM .
JOURNAL OF ANTIBIOTICS, 1988, 41 (08) :1074-1084
[2]   AN EFFICIENT SUBSTITUTE FOR THE ALPHA-AMINOADIPOYL MOIETY OF DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-VALINE IN THE ENZYMATIC-SYNTHESIS OF PENICILLINS [J].
BALDWIN, JE ;
ADLINGTON, RM ;
CRABBE, MJC ;
NOMOTO, T ;
SCHOFIELD, CJ .
TETRAHEDRON, 1987, 43 (18) :4217-4220
[3]   ENZYMATIC RING EXPANSION OF PENICILLINS TO CEPHALOSPORINS - SIDE-CHAIN SPECIFICITY [J].
BALDWIN, JE ;
ADLINGTON, RM ;
COATES, JB ;
CRABBE, MJC ;
KEEPING, JW ;
KNIGHT, GC ;
NOMOTO, T ;
SCHOFIELD, CJ ;
TING, HH .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1987, (05) :374-375
[4]   THE BIOSYNTHESIS OF PENICILLINS AND CEPHALOSPORINS [J].
BALDWIN, JE .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1990, 27 (01) :71-78
[5]   DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE SYNTHETASE (ACV SYNTHETASE) - A MULTIFUNCTIONAL ENZYME WITH BROAD SUBSTRATE-SPECIFICITY FOR THE SYNTHESIS OF PENICILLIN AND CEPHALOSPORIN PRECURSORS [J].
BANKO, G ;
DEMAIN, AL ;
WOLFE, S .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (09) :2858-2860
[6]   ENZYMATIC-SYNTHESIS OF THE PENICILLIN AND CEPHALOSPORIN NUCLEI FROM AN ACYCLIC PEPTIDE CONTAINING CARBOXYMETHYLCYSTEINE [J].
BOWERS, RJ ;
JENSEN, SE ;
LYUBECHANSKY, L ;
WESTLAKE, DWS ;
WOLFE, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (02) :607-613
[7]   COPURIFICATION AND CHARACTERIZATION OF DEACETOXYCEPHALOSPORIN-C SYNTHETASE HYDROXYLASE FROM CEPHALOSPORIUM-ACREMONIUM [J].
DOTZLAF, JE ;
YEH, WK .
JOURNAL OF BACTERIOLOGY, 1987, 169 (04) :1611-1618
[8]  
HUFMAN GW, 1988, ORG PREP PROC, V20, P497
[9]   PURIFICATION AND PARTIAL CHARACTERIZATION OF DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE SYNTHETASE FROM STREPTOMYCES-CLAVULIGERUS [J].
JENSEN, SE ;
WONG, A ;
ROLLINS, MJ ;
WESTLAKE, DWS .
JOURNAL OF BACTERIOLOGY, 1990, 172 (12) :7269-7271
[10]   PENICILLIN FORMATION BY CELL-FREE-EXTRACTS OF STREPTOMYCES-CLAVULIGERUS - BEHAVIOR OF AMINOADIPYL-MODIFIED ANALOGS OF THE NATURAL PEPTIDE PRECURSOR DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE (ACV) [J].
JENSEN, SE ;
WESTLAKE, DWS ;
BOWERS, RJ ;
INGOLD, CF ;
JOUANY, M ;
LYUBECHANSKY, L ;
WOLFE, S .
CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1984, 62 (12) :2712-2720
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