Earticle

초록

영어

The bacterial genus Streptomyces has long been appreciated for its ability to produce various kinds of medically important secondary metabolites, such as antibiotics, anti-tumour agents, immunosuppressants and enzyme inhibitors.Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive and anti-cancer compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene.Previously, we isolated and characterized the entire TMC biosynthetic gene cluster from Streptomyces sp. CK4412. Sequence information analysis of an 110kb DNA region revealed multi-modular type I polyketide synthases, type II thioesterase, various proteins for dialkylmaleic anhydride biosynthesis, regulatory proteins and several tailoring enzymes. Although both TMC and its close structural relative called Tautomycin (TM) compounds have similar inhibitory activities against two major serine/threonine protein phosphatise, PP1 and PP2A, the different linear polyketide moiety present in TMC and TM is believe to play a critical role because only TMC exhibits an immunosuppressant activity as well as a higher PP1 selectivity. To increase our understanding about the functional specificity, the targeted gene inactivation of various biosynthetic genes involved in the formation of a linear TMC polyketide moiety was performed, leading to the generation of several novel TMC analogs with different polyketide terminal region.

키워드

저자

• Sisun CHOI [ Department of Biological Engineering, Inha University, Incheon 402-751, Korea. ]
• David H. SHERMAN [ Life Sciences Institute and Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. ]
• Eung-Soo KIM [ Department of Biological Engineering, Inha University, Incheon 402-751, Korea. ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576