Earticle

초록

영어

Rapamycin is a macrocylic polyketide with immunosuppressive, antifungal, and anticancer activity. The production level of rapamycin in Streptomyces hygroscopicus ATCC29253 was enhanced by classical mutagenesis and metabolic engineering approach. This study describes the development of a novel highthroughput method for rapid screening of rapamycin-producing strains using agar diffusion method and metabolic engineering strategy to enhanced rapamycin production. Rapamycin production by a mutant strain UV2-2 induced by Ultraviolet (UV) mutagenesis was improved by approximately 3.2-fold compared to that of wild-type strain. The comparative analysis of gene expression and intracellular acyl-CoA pool between wild-type and the UV2-2 strains revealed that the increased production of rapamycin in UV2-2 was due to the prolonged expression of rapamycin biosynthetic genes but the low concentration of intracellular methylmalonyl-CoA was limiting the rapamycin biosynthesis in both strains. In an attempt to promote intracellular pool of methylmalonyl-CoA, propionyl-CoA carboxylase pathway was introduced into the mutant strain UV2-2 along with supplementation of methyloleate, resulting in an additional 1.7-fold improvement of rapamycin titers. These results demonstrate that the combined approach involving traditional mutagenesis and metabolic engineering can be successfully applied for the rapamycin-producing strain.

키워드

저자

• Young JI YOO [ Dept. of Chemistry and Nano Science, Ewha Womans University, ]
• Won Seok JUNG [ Dept. of Chemistry and Nano Science, Ewha Womans University ]
• Yeon-Hee BAN [ Dept. of Chemistry and Nano Science, Ewha Womans University, ]
• Eun Ji CHOI [ Dept. of Chemistry and Nano Science, Ewha Womans University, ]
• Eun Ae KIM [ Dept. of Chemistry and Nano Science, Ewha Womans University ]
• Eunji KIM [ Dept. of Chemistry and Nano Science, Ewha Womans University ]
• Yeo Joon YOON [ Dept. of Chemistry and Nano Science, Ewha Womans University, ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576