Genetic engineering of an industrial strain of Streptomyces clavuligerus  for further enhancement of clavulanic acid production

Aslihan Kurt KIZILDOĞAN; Güliz Vanli JACCARD; Alper MUTLU; İbrahim SERTDEMİR; Gülay ÖZCENGİZ

Makale detayları

Genetic engineering of an industrial strain of Streptomyces clavuligerus for further enhancement of clavulanic acid production

Yazarlar:

Aslihan Kurt KIZILDOĞAN | Güliz Vanli JACCARD | Alper MUTLU | İbrahim SERTDEMİR | Gülay ÖZCENGİZ

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Biology 2017 Vol.41 Issue 2, pp.342-353

Belge Tipi:

Makale

Yayın Tarihi:

3/2017

Belge Dili:

Türkçe

Document ID (Org No.):

2000811430

Sıklık:

İki Aylık

eISSN:

1303-6092

pISSN:

1300-0152

Özet:

 

An industrial clavulanic acid (CA) overproducer Streptomyces clavuligerus strain, namely DEPA, was engineered to further  enhance its CA production. Single or multiple copies of ccaR, claR (pathway-specific activators), and cas2 (CA synthase) genes under  the control of different promoters were introduced into this strain. CA titers of the resulting recombinants were analyzed by HPLC in  a dynamic fashion and compared to the vector-only controls and a wild-type strain of S. clavuligerus while their growth was monitored  throughout fermentation. The addition of an extra copy of ccaR, under control of its own promoter or constitutive ermE* promoter  (PermE*), led to 7.6- and 2.3-fold increased volumetric levels of CA in respective recombinants, namely the AK9 and ID3 strains. Its  highly stable multicopy expression by the glpF promoter (PglpF) provided up to 25.9-fold enhanced volumetric CA titers in the respective  recombinant, IDG3. claR expression controlled with its own promoter or ermE* and glpF-mediated amplification in an industrial  strain brought about only about 1.2-fold increase in the volumetric CA titers. An extra copy of cas2 integration with PermE* into the S.  clavuligerus DEPA genome led to 3.8-fold higher volumetric CA production by GV61. Conclusively, multicopy expression of ccaR under  PglpF can result in significantly improved industrial high-titer CA producers.

Makale detayları

Genetic engineering of an industrial strain of Streptomyces clavuligerus for further enhancement of clavulanic acid production

Yazarlar: Aslihan Kurt KIZILDOĞAN | Güliz Vanli JACCARD | Alper MUTLU | İbrahim SERTDEMİR | Gülay ÖZCENGİZ

Yayıncı: TUBITAK

Dergi: Turkish Journal of Biology 2017 Vol.41 Issue 2, pp.342-353

Belge Tipi: Makale

Yayın Tarihi: 3/2017

Belge Dili: Türkçe

Document ID (Org No.): 2000811430

Sıklık: İki Aylık

eISSN: 1303-6092

pISSN: 1300-0152

Sayı

Yazarlar:

Aslihan Kurt KIZILDOĞAN | Güliz Vanli JACCARD | Alper MUTLU | İbrahim SERTDEMİR | Gülay ÖZCENGİZ

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Biology 2017 Vol.41 Issue 2, pp.342-353

Belge Tipi:

Makale

Yayın Tarihi:

3/2017

Belge Dili:

Türkçe

Document ID (Org No.):

2000811430

Sıklık:

İki Aylık

eISSN:

1303-6092

pISSN:

1300-0152