Enhanced rapamycin production in Streptomyces hygroscopicus by integrative expression of aveR, a LAL family transcriptional regulator

Huang, Minhong; Li, Min; Feng, Zhi-Xiang; Liu, Yang; Chu, Yiwen; Tian, Yongqiang

doi:10.1007/s11274-011-0673-y

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…In addition, many regulatory genes can also be expressed in other strains and can influence antibiotic production by heterologous expression combined with other methods. For example, the integration of aveR, orfX, or afsR in the chromosomes of S. hygroscopicus promoted rapamycin production by approximately 3.8-fold, 1.2-fold or slightly, respectively (Huang et al 2011). Currently, we can effectively influence antibiotic production by manipulating regulatory genes involved in pathway-specific regulation or pleiotropic regulation in Streptomyces.…”

Section: Discussionmentioning

confidence: 99%

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces

Hou

Zhang

et al. 2017

3 Biotech

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The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators. The study of regulatory genes that influence antibiotic biosynthesis in Streptomyces spp. not only provides a theoretical basis for antibiotic biosynthesis in Streptomyces but also helps to increase the yield of antibiotics via molecular manipulation of these regulatory genes. Currently, more and more emphasis is being placed on the regulatory genes of antibiotic biosynthetic gene clusters in Streptomyces spp., and many studies on these genes have been performed to improve the yield of antibiotics in Streptomyces. This paper lists many antibiotic biosynthesis regulatory genes in Streptomyces spp. and focuses on frequently investigated regulatory genes that are involved in pathway-specific regulation and pleiotropic regulation and their applications in genetic engineering.

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Section: Discussionmentioning

confidence: 99%

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces

Hou

Zhang

et al. 2017

3 Biotech

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“…Sirolimus and everolimus are produced by the methods of biotechnological fermentation of bacterial species in the genus Streptomyces, particularly Streptomyces hygroscopicus, generating the antibiotic in medium that contains flour, dextrin, glycerol, L-lysine, KH 2 PO 4 , K 2 HPO 4 , (NH 4 ) 2 SO 4 , and trace elements [119][120][121][122][123][124][125][126]. Synthesis of temsirolimus from rapamycin is patented [127].…”

Section: Mammalian Target Of Rapamycin Inhibitorsmentioning

confidence: 99%

Immunopharmacological Drugs

Vardanyan

Hruby

2016

Synthesis of Best-Seller Drugs

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An overview of rapamycin: from discovery to future perspectives

Yoo

Kim

Park

et al. 2017

Journal of Industrial Microbiology and Biotechnology

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Rapamycin is an immunosuppressive metabolite produced from several actinomycete species. Besides its immunosuppressive activity, rapamycin and its analogs have additional therapeutic potentials, including antifungal, antitumor, neuroprotective/neuroregenerative, and lifespan extension activities. The core structure of rapamycin is derived from (4R,5R)-4,5-dihydrocyclohex-1-ene-carboxylic acid that is extended by polyketide synthase. The resulting linear polyketide chain is cyclized by incorporating pipecolate and further decorated by post-PKS modification enzymes. Herein, we review the discovery and biological activities of rapamycin as well as its mechanism of action, mechanistic target, biosynthesis, and regulation. In addition, we introduce the many efforts directed at enhancing the production of rapamycin and generating diverse analogs and also explore future perspectives in rapamycin research. This review will also emphasize the remarkable pilot studies on the biosynthesis and production improvement of rapamycin by Dr. Demain, one of the world's distinguished scientists in industrial microbiology and biotechnology.

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Enhanced rapamycin production in Streptomyces hygroscopicus by integrative expression of aveR, a LAL family transcriptional regulator

Abstract: Rapamycin produced by Streptomyces hygroscopicus displays immunosuppressive, antifungal, antitumor, anti-inflammatory and neuro-regenerative properties.

Cited by 6 publications

References 21 publications

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces

Immunopharmacological Drugs

An overview of rapamycin: from discovery to future perspectives

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