Transcriptional regulation and increased production of asukamycin in engineered Streptomyces nodosus subsp. asukaensis strains

Applied Microbiology and Biotechnology
Pengfei XieTaifo Mahmud

Abstract

Asukamycin, a member of the manumycin family of antibiotics, exhibits strong antibacterial, antifungal, and antineoplastic activities. However, its production in the wild-type strain of Streptomyces nodosus subsp. asukaensis ATCC 29757 is relatively low. Recently, the biosynthetic gene cluster for asukamycin was identified in the producing organism, and among the 36 genes reported in the cluster, six (asuR1-asuR6) were proposed to encode proteins that function as transcriptional regulators. In order to investigate their involvement in asukamycin biosynthesis and to engineer mutant strains of S. nodosus that are able to produce large amounts of asukamycin, we carried out in vivo gene inactivation, transcriptional analysis of the biosynthetic genes in the mutants, and gene duplication in the producing strain of S. nodosus. The results show that two of the putative regulatory genes (asuR1 and asuR5) are critical for asukamycin biosynthesis, whereas others regulate the pathway at various levels. Overexpression of a gene cassette harboring asuR1, asuR2, asuR3, and asuR4 in S. nodosus resulted in changes in morphology of the producing strain and an approximately 14-fold increase of asukamycin production. However, overexpression of th...Continue Reading

References

Sep 1, 1976·The Journal of Antibiotics·S OmuraY Takahashi
Feb 1, 1987·The Journal of Antibiotics·M MatsumotoT Nakashima
Sep 1, 1995·Molecular Microbiology·D M SitnikovT O Baldwin
Aug 27, 1996·Biochemistry·I BaikalovR E Dickerson
Aug 23, 2000·Molecular & General Genetics : MGG·A BurgerW Wohlleben
Apr 9, 2005·The Journal of Antibiotics·János Bérdy
Jun 10, 2005·Microbiology and Molecular Biology Reviews : MMBR·Juan L RamosRaquel Tobes
Apr 18, 2007·Cellular and Molecular Life Sciences : CMLS·G HornH R Kalbitzer
Aug 12, 2009·Chembiochem : a European Journal of Chemical Biology·Takuya ItoTaifo Mahmud
Jan 22, 2010·Applied Microbiology and Biotechnology·Yihua ChenBen Shen
May 15, 2010·Journal of Microbiology and Biotechnology·Yunlong HeZixin Deng
Jun 5, 2010·The Journal of Biological Chemistry·Zhe RuiTin-Wein Yu

❮ Previous
Next ❯

Citations

Jul 9, 2013·Science China. Life Sciences·Yanyan ZhangHuarong Tan
May 20, 2014·Chembiochem : a European Journal of Chemical Biology·Kateřina PetříčkováMiroslav Petříček
Aug 2, 2017·Biotechnology and Applied Biochemistry·Bo ZhangYu-Guo Zheng
Sep 3, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takuya Ito
Oct 3, 2018·Applied Microbiology and Biotechnology·Wanli LuTaifo Mahmud

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.