Disruption of negative regulators (SP_nsdA and SP_nsdB) in Streptomyces peucetius causes doxorubicin overproduction

Jun-Ho Cho; Mi-Kyeong Kim; Kyoung-Hee Kwon; Kisup Ahn; Jong Hwa Jang; Joo-Ho Lee; Tae-Jin Oh*

doi:10.5897/AJMR2014.6895

African Journal of
Microbiology Research

Abbreviation: Afr. J. Microbiol. Res.
Language: English
ISSN: 1996-0808
DOI: 10.5897/AJMR
Start Year: 2007
Published Articles: 5233

Full Length Research Paper

Disruption of negative regulators (SP_nsdA and SP_nsdB) in Streptomyces peucetius causes doxorubicin overproduction

Jun-Ho Cho

Jun-Ho Cho
Department of Pharmaceutical Engineering, SunMoon University, #100, Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Korea
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Mi-Kyeong Kim

Mi-Kyeong Kim
Department of Pharmaceutical Engineering, SunMoon University, #100, Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Korea
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Kyoung-Hee Kwon

Kyoung-Hee Kwon
Department of Health Administration, Baekseok Culture University, #393, Anseo-dong, Dongnam-gu, Cheonan-si, Chungnam 330-705, Korea
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Kisup Ahn

Kisup Ahn
Department of Health Administration, Baekseok Culture University, #393, Anseo-dong, Dongnam-gu, Cheonan-si, Chungnam 330-705, Korea
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Jong Hwa Jang

Jong Hwa Jang
Department of Dental Hygiene, Hanseo University, #46, Hanseo 1-ro, Haemi-myun, Seosan-si, Chungnam 356-706, Korea
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Joo-Ho Lee

Joo-Ho Lee
Department of Pharmaceutical Engineering, SunMoon University, #100, Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Korea
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Tae-Jin Oh*

Tae-Jin Oh*
Department of Pharmaceutical Engineering, SunMoon University, #100, Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Korea
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Article Number - 0DFC59149579
Vol.8(51), pp. 3969-3975 , December 2014
https://doi.org/10.5897/AJMR2014.6895

Received: 12 May 2014
Accepted: 28 November 2014
Published: 17 December 2014

Abstract

Pathway-specific regulatory genes generally participate in the secondary metabolites-related biosynthesis process. The genes nsdA and nsdB were reported to have a negative effect on the production of actinorhodin, prodigiosin and calcium-dependent antibiotic from Streptomyces coelicolor. In this study, we searched for similar genes in the Streptomyces peucetius genome, the doxorubicin producer. Amino acid sequence similarity between SC_NsdA and SP4635 (SP_NsdA) was 88.1%, and between SC_NsdB and SP1750 (SP_NsdB) was 78.4%. High performance liquid chromatography (HPLC) analysis revealed that the disruption of SP_nsdA and SP_nsdB significantly increased doxorubicin production by 2.07 and 1.74-fold, respectively. The SP_nsdA and SP_nsdB disruption mutants produced more yellow pigment and early aerial mycelium than did the original wild-type strain. These results show that SP_nsdA and SP_nsdB negatively affected doxorubicin production and morphological differentiation in S. peucetius.