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- Title
Ribosome engineering and fermentation optimization leads to overproduction of tiancimycin A, a new enediyne natural product from <italic>Streptomyces</italic> sp. CB03234.
- Authors
Liu, Ling; Pan, Jian; Wang, Zilong; Yan, Xiaohui; Yang, Dong; Zhu, Xiangcheng; Shen, Ben; Duan, Yanwen; Huang, Yong
- Abstract
Tiancimycin (TNM) A, a recently discovered enediyne natural product from <italic>Streptomyces</italic> sp. CB03234, showed rapid and complete killing of cancer cells and could be used as a payload in antibody drug conjugates. The low yield of TNM A in the wild-type strain promoted us to use ribosome engineering and fermentation optimization for its yield improvement. The <italic>Streptomyces</italic> sp. CB03234-R-16 mutant strain with a L422P mutation in RpoB, the RNA polymerase <italic>β</italic>-subunit, was obtained from the rifamycin-resistant screening. After fermentation optimization, the titers of TNM A in <italic>Streptomyces</italic> sp. CB03234-R-16 reached to 22.5 ± 3.1 mg L−1 in shaking flasks, and 13 ± 1 mg L−1 in 15 L fermentors, which were at least 40-fold higher than that in the wild-type strain (~ 0.3 mg L−1). Quantitative real-time RT-PCR revealed markedly enhanced expression of key genes encoding TNM A biosynthetic enzymes and regulators in <italic>Streptomyces</italic> sp. CB03234-R-16. Our study should greatly facilitate the future efforts to develop TNM A into a clinical anticancer drug.
- Subjects
ENEDIYNES synthesis; STREPTOMYCES; FERMENTATION; PROTEIN engineering; ANTINEOPLASTIC agents
- Publication
Journal of Industrial Microbiology & Biotechnology, 2018, Vol 45, Issue 3, p141
- ISSN
1367-5435
- Publication type
Article
- DOI
10.1007/s10295-018-2014-8