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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 Streptomyces sp. CB03234-R-16 mutant strain with a L422P mutation in RpoB, the RNA polymerase \u03b2-subunit, was obtained from the rifamycin-resistant screening. After fermentation optimization, the titers of TNM A in Streptomyces sp. CB03234-R-16 reached to 22.5\u00a0\u00b1\u00a03.1\u00a0mg L\u22121 in shaking flasks, and 13\u00a0\u00b1\u00a01\u00a0mg\u00a0L\u22121 in 15\u00a0L fermentors, which were at least 40-fold higher than that in the wild-type strain (~\u00a00.3\u00a0mg\u00a0L\u22121). Quantitative real-time RT-PCR revealed markedly enhanced expression of key genes encoding TNM A biosynthetic enzymes and regulators in Streptomyces sp. CB03234-R-16. Our study should greatly facilitate the future efforts to develop TNM A into a clinical anticancer drug.<\/jats:p>","DOI":"10.1007\/s10295-018-2014-8","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T07:33:44Z","timestamp":1517556824000},"page":"141-151","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Ribosome engineering and fermentation optimization leads to overproduction of tiancimycin A, a new enediyne natural product from <i>Streptomyces<\/i> sp. 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