Identification of TmcN as a pathway-specific positive regulator of tautomycetin biosynthesis in Streptomyces sp. CK4412
- 1 October 2008
- journal article
- Published by Microbiology Society in Microbiology
- Vol. 154 (10), 2912-2919
- https://doi.org/10.1099/mic.0.2008/018903-0
Abstract
Tautomycetin (TMC) is a novel activated T-cell-specific immunosuppressive compound with a unique structure, containing an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. A 3 kb gene, tmcN, with a deduced product of 1029 amino acid residues, located on the 3'-terminus of an approximately 70 kb contiguous TMC biosynthetic gene cluster, was found to have amino acid sequence homology with bacterial regulatory proteins. In silico database comparisons revealed that TmcN belongs to the large ATP-binding regulators of the LuxR protein family. Gene disruption of tmcN from the Streptomyces sp. CK4412 chromosome resulted in significantly reduced antifungal activity against Aspergillus niger, as well as the absence of TMC. In addition, complementation by an integrative plasmid carrying tmcN restored TMC biosynthesis, strongly suggesting that TmcN is a positive regulator of TMC biosynthesis. Gene expression analysis by RT-PCR of the TMC biosynthetic genes revealed that a TmcN mutant strain exhibited reduced expression levels for most of the biosynthetic genes except for its own tmcN. It is thus suggested that TmcN is a pathway-specific positive regulator that activates transcription of the TMC biosynthetic pathway genes in Streptomyces sp. CK4412.Keywords
This publication has 32 references indexed in Scilit:
- Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412Microbiology, 2007
- Intraspecific Variability of the Terminal Inverted Repeats of the Linear Chromosome of Streptomyces ambofaciensJournal of Bacteriology, 2006
- Regulation of secondary metabolism in streptomycetesCurrent Opinion in Microbiology, 2005
- Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Kitasatospora setae , a bafilomycin B 1 producerArchiv für Mikrobiologie, 2004
- Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathwayCell Chemical Biology, 2000
- A subfamily of MalT-related ATP-dependent regulators in the LuxR familyMicrobiology, 1999
- Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthaseGene, 1996
- Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp.Gene, 1992
- Multilevel regulation of Streptomyces differentiationTrends in Genetics, 1989
- A new antibiotic, tautomycetin.The Journal of Antibiotics, 1989