Recent biotechnological interventions for developing improved penicillin G acylases

被引：6

作者：

Rajendhran, J ^{[1
]}

Gunasekaran, P ^{[1
]}

机构：

[1] Madurai Kamaraj Univ, Sch Biol Sci, Ctr Excellence Genom Sci, Dept Microbial Technol, Madurai 625021, Tamil Nadu, India

来源：

JOURNAL OF BIOSCIENCE AND BIOENGINEERING | 2004年 / 97卷 / 01期

关键词：

penicillin acylase; beta-lactam antibiotics; post-translational processing; enzyme stabilization; protein engineering; directed evolution;

D O I：

暂无

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：

Penicillin G acylase (PAC; EC 3.5.1.11) is the key enzyme used in the industrial production of beta-lactam antibiotics. This enzyme hydrolyzes the side chain of penicillin G and related P-lactam antibiotics releasing 6-amino penicillanic acid (6-APA), which is the building block in the manufacture of semisynthetic penicillins. PAC from Escherichia coli strain ATCC 11105, Bacillus megaterium strain ATCC 14945 and mutants of these two strains is currently used in industry. Genes encoding for PAC from various bacterial sources have been cloned and overexpressed with significant improvements in transcription, translation and post-translational processing. Recent developments in enzyme engineering have shown that PAC can be modified to gain conformational stability and desired functionality. This review provides an overview of recent advances in the production, stabilization and application of PAC, highlighting the recent biotechnological approaches for the improved catalysis of PAC.

引用

页码：1 / 13

页数：13

共 113 条

[1] Role of αArg145 and βArg263 in the active site of penicillin acylase of Escherichia coli [J].

Alkema, WBL ;

Prins, AK ;

de Vries, E ;

Janssen, DB .

BIOCHEMICAL JOURNAL, 2002, 365 :303-309

[2] The role of hydrophobic active-site residues in substrate specificity and acyl transfer activity of penicillin acylase [J].

Alkema, WBL ;

Dijkhuis, AJ ;

de Vries, E ;

Janssen, DB .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (08) :2093-2100

[3] Characterization of the β-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies [J].

Alkema, WBL ;

Hensgens, CMH ;

Kroezinga, EH ;

de Vries, E ;

Floris, R ;

van der Laan, JM ;

Dijkstra, BW ;

Janssen, DB .

PROTEIN ENGINEERING, 2000, 13 (12) :857-863

[4]

Azevedo AM, 1999, J CHEM TECHNOL BIOT, V74, P1110, DOI 10.1002/(SICI)1097-4660(199911)74:11<1110::AID-JCTB149>3.0.CO

[5]

2-B

[6] COMPLETE NUCLEOTIDE-SEQUENCE OF THE PENICILLIN ACYLASE GENE FROM KLUYVERA-CITROPHILA [J].

BARBERO, JL ;

BUESA, JM ;

DEBUITRAGO, GG ;

MENDEZ, E ;

PEREZARANDA, A ;

GARCIA, JL .

GENE, 1986, 49 (01) :69-80

[7] A common export pathway for proteins binding complex redox cofactors? [J].

Berks, BC .

MOLECULAR MICROBIOLOGY, 1996, 22 (03) :393-404

[8] A PROTEIN CATALYTIC FRAMEWORK WITH AN N-TERMINAL NUCLEOPHILE IS CAPABLE OF SELF-ACTIVATION [J].

BRANNIGAN, JA ;

DODSON, G ;

DUGGLEBY, HJ ;

MOODY, PCE ;

SMITH, JL ;

TOMCHICK, DR ;

MURZIN, AG .

NATURE, 1995, 378 (6555) :416-419

[9] Cross-linked aggregates of penicillin acylase:: robust catalysts for the synthesis of β-lactam antibiotics [J].

Cao, L ;

van Langen, LM ;

van Rantwijk, F ;

Sheldon, RA .

JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, 2001, 11 (4-6) :665-670

[10] PURIFICATION AND PROPERTIES OF PENICILLIN AMIDASE FROM BACILLUS MEGATERIUM [J].

CHIANG, C ;

BENNETT, RE .

JOURNAL OF BACTERIOLOGY, 1967, 93 (01) :302-&

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