Applications of gene replacement technology to Streptomyces clavuligerus strain development for clavulanic acid production

Applied and Environmental Microbiology
A S ParadkarS E Jensen

Abstract

Cephamycin C production was blocked in wild-type cultures of the clavulanic acid-producing organism Streptomyces clavuligerus by targeted disruption of the gene (lat) encoding lysine epsilon-aminotransferase. Specific production of clavulanic acid increased in the lat mutants derived from the wild-type strain by 2- to 2.5-fold. Similar beneficial effects on clavulanic acid production were noted in previous studies when gene disruption was used to block the production of the non-clavulanic acid clavams produced by S. clavuligerus. Therefore, mutations in lat and in cvm1, a gene involved in clavam production, were introduced into a high-titer industrial strain of S. clavuligerus to create a double mutant with defects in production of both cephamycin C and clavams. Production of both cephamycin C and non-clavulanic acid clavams was eliminated in the double mutant, and clavulanic acid titers increased about 10% relative to those of the parental strain. This represents the first report of the successful use of genetic engineering to eliminate undesirable metabolic pathways in an industrial strain used for the production of an antibiotic important in human medicine.

References

Sep 1, 1985·Journal of General Microbiology·J S FeitelsonD A Hopwood

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Citations

Jul 27, 2007·Applied Microbiology and Biotechnology·Jian-Ting ZhengKe-Qian Yang
Aug 17, 2010·Applied Microbiology and Biotechnology·Ju Yeon SongKye Joon Lee
Oct 12, 2010·Applied Microbiology and Biotechnology·Xianpu NiHuanzhang Xia
Mar 13, 2012·Applied Microbiology and Biotechnology·Di HuangYunlin Chen
Nov 23, 2007·Natural Product Reports·J Stefan RokemJens Nielsen
Mar 23, 2012·Canadian Journal of Microbiology·Sarah Goomeshi Nobary, Susan E Jensen
Jan 9, 2009·Bioscience, Biotechnology, and Biochemistry·Sae-Jin KimChan-Wha Kim
Dec 12, 2012·Biotechnology Advances·Gulay Ozcengiz, Arnold L Demain
Jul 15, 2015·Biotechnology Progress·Claudia SánchezSilvia Ochoa
Apr 16, 2003·Critical Reviews in Biotechnology·Ashish ParadkarDiane Stassi
Jul 25, 2020·Protein and Peptide Letters·Eser ÜnsaldıGülay Özcengiz

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