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Titolo:
PRECURSOR FLUX CONTROL THROUGH TARGETED CHROMOSOMAL INSERTION OF THE LYSINE EPSILON-AMINOTRANSFERASE (LAT) GENE IN CEPHAMYCIN C BIOSYNTHESIS
Autore:
MALMBERG LH; HU WS; SHERMAN DH;
Indirizzi:
UNIV MINNESOTA,DEPT MICROBIOL ST PAUL MN 55108 UNIV MINNESOTA,DEPT MICROBIOL ST PAUL MN 55108 UNIV MINNESOTA,DEPT CHEM ENGN & MAT SCI MINNEAPOLIS MN 55455 UNIV MINNESOTA,INST BIOL PROC TECHNOL ST PAUL MN 55108
Titolo Testata:
Journal of bacteriology
fascicolo: 21, volume: 175, anno: 1993,
pagine: 6916 - 6924
SICI:
0021-9193(1993)175:21<6916:PFCTTC>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
STREPTOMYCES-CLAVULIGERUS; CEPHALOSPORIN BIOSYNTHESIS; ANTIBIOTIC BIOSYNTHESIS; NUCLEOTIDE-SEQUENCE; SYNTHETASE; CLONING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
L.H. Malmberg et al., "PRECURSOR FLUX CONTROL THROUGH TARGETED CHROMOSOMAL INSERTION OF THE LYSINE EPSILON-AMINOTRANSFERASE (LAT) GENE IN CEPHAMYCIN C BIOSYNTHESIS", Journal of bacteriology, 175(21), 1993, pp. 6916-6924

Abstract

Targeted gene insertion methodology was used to study the effect of perturbing alpha-aminoadipic acid precursor flux on the overall production rate of beta-lactam biosynthesis in Streptomyces clavuligerus. A high-copy-number plasmid containing the lysine epsilon-aminotransferasegene (lat) was constructed and used to transform S. clavuligerus. Theresulting recombinant strain (LHM100) contained an additional complete copy of lat located adjacent to the corresponding wild-type gene in the chromosome. Biological activity and production levels of beta-lactam antibiotics were two to five times greater than in wild-type S. clavuligerus. Although levels of lysine epsilon-aminotransferase were elevated fourfold in LHM100, the level of ACV synthetase, whose gene is located just downstream of lat, remained unchanged. These data stronglysupport the notion that direct perturbation of alpha-aminoadipic acidprecursor flux resulted in increased antibiotic production. This strategy represents a successful application of metabolic engineering based on theoretical predictions of precursor flux in a secondary metabolic pathway.

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Documento generato il 01/10/20 alle ore 01:24:43