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题名: Effect of overexpression of endogenous and exogenous Streptomyces antibiotic regulatory proteins on tacrolimus (FK506) production in Streptomyces sp KCCM11116P
作者: Chen, Chao1;  Zhao, Xinqing1, 2;  Chen, Liangyu1;  Jin, Yingyu3;  Zhao, Zongbao K.4;  Suh, Joo-Won3
刊名: RSC ADVANCES
发表日期: 2015
DOI: 10.1039/c4ra15038d
卷: 5, 期:21, 页:15756-15762
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
英文摘要: With the development of synthetic biology and systems biology, overproduction of biomolecules can be achieved by manipulation of regulatory proteins from various sources. FK506 (tacrolimus) is a 23-membered macrolide antibiotic and an important immunosuppressant. Overproduction of FK506 has been achieved by the manipulation of regulatory genes that are located inside the biosynthetic gene cluster, however, little is known on the effect of other regulators on FK506 production. In this study, the effects of three Streptomyces antibiotic regulatory proteins (SARPs) on FK506 production were investigated. These SARPs include bulZ and bulY that are cloned from a FK506 producer Streptomyces sp. KCCM11116P, and one novel SARP family regulatory protein Sx5140 that was obtained from a marine streptomycete S. xinghaiensis. The production titer of the engineered strains exhibited a higher production level compared to that in the control strain (227.99 mg L-1), and overexpression of bulZ resulted in the highest FK506 titer (365.59 mg L-1), which is 1.6-fold of that of the control. Real-time PCR analysis showed that overexpression of bulZ and bulY resulted in increased transcription of tsuR1 which is the gamma-butyrolactone receptor. Variation of transcription levels of fkbN, the positive regulator of FK506 biosynthesis, as well as fkbG, fkbH, fkbI, tcsA, tcsB, tcsD and fkbQ genes that are involved in the FK506 biosynthesis were observed in the SARP overexpression strains compared to those in the control strain. Our results demonstrate the promising potential to utilize alternative regulatory proteins including both endogenous and exogenous ones to enhance the production of useful compounds in microbial strains.
关键词[WOS]: SECONDARY METABOLISM ;  SIGNALING MOLECULES ;  POLYKETIDE SYNTHASE ;  MARINE SEDIMENT ;  DRAFT GENOME ;  BIOSYNTHESIS ;  TSUKUBAENSIS ;  IMMUNOSUPPRESSANT ;  GENES ;  DAUNORUBICIN
语种: 英语
WOS记录号: WOS:000349524700001
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146013
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Dalian Univ Technol, Sch Life Sci & Biotechnol, Dalian 116024, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China
3.Myongji Univ, Div Biosci & Bioinformat, Yongin 449728, South Korea
4.Chinese Acad Sci, Dept Biotechnol, Dalian Inst Chem Phys, Dalian 116023, Peoples R China

Recommended Citation:
Chen, Chao,Zhao, Xinqing,Chen, Liangyu,et al. Effect of overexpression of endogenous and exogenous Streptomyces antibiotic regulatory proteins on tacrolimus (FK506) production in Streptomyces sp KCCM11116P[J]. RSC ADVANCES,2015,5(21):15756-15762.
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