A 2-STEP ENZYMATIC-SYNTHESIS OF DIPEPTIDES

被引:21
作者
SCHWARZ, A
WANDREY, C
STEINKE, D
KULA, MR
机构
[1] FORSCHUNGSZENTRUM JULICH, RES CTR, INST BIOTECHNOL, W-5170 JULICH 1, GERMANY
[2] UNIV DUSSELDORF, RES CTR JULICH, INST ENZYME TECHNOL, W-5170 JULICH, GERMANY
关键词
ENZYMATIC SYNTHESIS; CONTINUOUS PRODUCTION; ANION-EXCHANGE; PEPTIDE-AMIDASE;
D O I
10.1002/bit.260390203
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
A simple system is introduced to produce dipeptides continuously by enzyme catalyzed condensation of amino acid esters and amino acid amides. Synthesis of N-terminal free dipeptide-amides is achieved by means of carboxypeptidase Y. The peptide-amide is deamidated utilizing a newly isolated peptide-amidase. Separation of substrates and products is accomplished by anion-exchange chromatography. Modeling of the reactions shows that the two reactions have to be carried out in a cascade of two reactors in order to prevent hydrolysis of the peptide by the carboxypeptidase. Continuous production of Kyotorphin (H-TyrArg-OH) with a space-time yield of 257 g/L d shows the feasibility of this concept.
引用
收藏
页码:132 / 140
页数:9
相关论文
共 13 条
[1]  
BLACKLOCK TJ, 1987, PEPTIDES, V9, P39
[2]   CHEMICALLY MODIFIED CARBOXYPEPTIDASE-Y WITH INCREASED AMIDASE ACTIVITY [J].
BREDDAM, K .
CARLSBERG RESEARCH COMMUNICATIONS, 1984, 49 (05) :535-554
[3]   SERINE CARBOXYPEPTIDASES - A REVIEW [J].
BREDDAM, K .
CARLSBERG RESEARCH COMMUNICATIONS, 1986, 51 (02) :83-128
[4]   PEPTIDE-SYNTHESIS AND DEAMIDATION WITH CHEMICALLY MODIFIED IMMOBILIZED CARBOXYPEPTIDASE-Y [J].
CRAMER, SM ;
HORVATH, C .
ENZYME AND MICROBIAL TECHNOLOGY, 1989, 11 (02) :74-79
[5]   DEMONSTRATION OF ACYL-ENZYME MECHANISM FOR HYDROLYSIS OF PEPTIDES AND ANILIDES BY CHYMOTRYPSIN [J].
FASTREZ, J ;
FERSHT, AR .
BIOCHEMISTRY, 1973, 12 (11) :2025-2034
[6]   CONTINUOUS PRODUCTION OF KYOTORPHIN [J].
FLORSHEIMER, A ;
KULA, MR ;
SCHUTZ, HJ ;
WANDREY, C .
BIOTECHNOLOGY AND BIOENGINEERING, 1989, 33 (11) :1400-1405
[7]  
HERRMANN G, 1991, BIOTECHNOL APPL BIOC, V13, P346
[8]   CATALYTIC ACTIVITY AND DENATURATION OF ENZYMES IN WATER ORGANIC COSOLVENT MIXTURES - ALPHA-CHYMOTRYPSIN AND LACCASE IN MIXED WATER ALCOHOL, WATER GLYCOL AND WATER FORMAMIDE SOLVENTS [J].
MOZHAEV, VV ;
KHMELNITSKY, YL ;
SERGEEVA, MV ;
BELOVA, AB ;
KLYACHKO, NL ;
LEVASHOV, AV ;
MARTINEK, K .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 184 (03) :597-602
[9]   APPLICATION OF CARBOXYPEPTIDASE-C FOR PEPTIDE-SYNTHESIS [J].
STEINKE, D ;
KULA, MR .
ENZYME AND MICROBIAL TECHNOLOGY, 1990, 12 (11) :836-840
[10]   FORMATION OF PEPTIDE-BONDS BY CARBOXYPEPTIDASE-C FROM ORANGE LEAVES [J].
STEINKE, D ;
SCHWARZ, A ;
WANDREY, C ;
KULA, MR .
ENZYME AND MICROBIAL TECHNOLOGY, 1991, 13 (03) :262-266