Isolation and Characterization of the Biosynthetic and Regulatory Genes for Tautomycetin, a Linear Polyketide T Cell-Specific Immunomodulator from Streptomyces sp. CK4412
The bacterial genus Streptomyces is well known for its ability to produce a wide variety of secondary metabolites, including medically important products such as antibiotics, anti-tumor agents, immunosuppressants, and enzyme inhibitors. Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Using a Streptomyces polyketide methylmalonyl-CoA acyltransferase gene as a probe, three overlapping cosmids were isolated from the genomic library of TMC-producing Streptomyces sp. CK4412. Sequence information of an approximately 70 kb contiguous DNA region revealed two multi-modular type I polyketide synthases (PKSs) and twelve additional gene including a regulatory gene products presumably involved in TMC biosynthesis. The deduced roles for most of the TMC PKS catalytic domains were consistent with the expected functions necessary for TMC chain elongation and processing. In addition, disruption of a putative TMC acyl-CoA transferase gene, located upstream of the PKS gene locus, completely abolished TMC biosynthesis. Taken together, these data provide strong supporting evidence that the cloned gene cluster identified in this study is responsible for TMC biosynthesis in Streptomyces sp. CK4412, and sets the stage for detailed genetic and biochemical studies on the biosynthesis of this important metabolite.
저자
Yoon-Ah Hur [ Department of Biological Engineering, Inha University ]
Si-Sun Choi [ Department of Biological Engineering, Inha University ]
Eung-Soo Kim [ Department of Biological Engineering, Inha University ]
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
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