Asian Federation of Biotechnology International Symposium :Co-organized by Asian Federation of Biotechnology : Chairs: Duk Jae OH(Sejong University, Korea), Virendra S. BISARIA(Indian Institute of Technology Delhi, India)
Streptomyces Genome Engineering for Biosynthesis and Regulation of a Novel Immunosuppressant Linear Polyketide, Tautomycetin
cell‐specific immunosuppressive compound with novel mode of pharmacological action both in vivo and in vitro, whose chemical structure was shown to be identical to a previously‐reported antifungal compound named tautomycetin (TMC). Inhibition of T cell proliferation with TMC was observed at concentrations 100‐fold lower than those needed to achieve maximal inhibition with cyclosporin A (CsA). TMC is classified as a type I polyketide derived metabolite based on its chemical structure, specifically the presence of a linear branched‐chain fatty acid‐like moiety. The unique chemical structure of TMC that includes an ester bond linkage between a cyclic C8 dialkylmaleic anhydride at one terminus, and a linear polyketide chain bearing a terminal alkene at the other, indicated that the corresponding biosynthetic pathway features a number of unique biochemical steps with significant potential for generating novel TMC derivatives. Sequence information revealed two multi‐modular type I polyketide synthases (PKSs) and several additional 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, a tmcN with a deduced product of 1,029 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 a bacteria Large ATP‐binding regulators of the LuxR (LAL) protein family. Gene disruption of tmcN from the Streptomyces sp. CK4412 chromosome resulted in significantly reduced antifungal activity as well as the absence of TMC. In addition, overexpression of tmcN stimulated TMC biosynthesis, strongly suggesting that TmcN is a pathway‐specific positive‐regulator that activates transcription of the TMC biosynthetic pathway genes in Streptomyces sp. CK4412.
저자
Eung-Soo KIM [ Department of Biological Engineering, Inha University University, Incheon, Korea. ]
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
이 법인은 생물 공학의 발전과 보급에 이바지하고, 회원 상호 간의 연구 협력과 친목을 도모함을 목적으로 한다
1. 생물공학 분야의 발전을 위한 연구 협력
2. 생물공학의 실용화를 촉진시키기 위한 산학 협동
3. 학술연구 발표회, 강연회, 연수회 등 학술활동의 개최
4. 국,영문 학술지,소식지,학술회의 Proceedings 및 학술도서의 발간
5. 생물공학 발전을 위한 정책 건의
6. 기타 국제 교류 등 본 학회의 목적 달성을 위한 제반 활동