The heterologous production of iso-migrastatin (iso-MGS) was successfully demonstrated in an engineered S. lividans SB11002 strain, which was derived from S. lividans K4-114, following introduction of pBS11001, which harbored the entire mgs biosynthetic gene cluster. However, under similar fermentation conditions, the iso-MGS titer in the engineered strain was significantly lower than that in the native producer - Streptomyces platensis NRRL 18993. To circumvent the problem of low iso-MGS titers and to expand the utility of this heterologous system for iso-MGS biosynthesis and engineering, systematic optimization of the fermentation medium was carried out. The effects of major components in the cultivation medium, including carbon, organic and inorganic nitrogen sources, were investigated using a single factor optimization method. As a result, sucrose and yeast extract were determined to be the best carbon and organic nitrogen sources, resulting in optimized iso-MGS production. Conversely, all other inorganic nitrogen sources evaluated produced various levels of inhibition of iso-MGS production. The final optimized R2YE production medium produced iso-MGS with a titer of 86.5 mg/L, about 3.6-fold higher than that in the original R2YE medium, and 1.5 fold higher than that found within the native S. platensis NRRL 18993 producer.

中文翻译：

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通过优化发酵条件提高工程改造的 Streptomyces lividans SB11002 菌株的异移行他汀滴度。

在引入包含整个 mgs 生物合成基因簇的 pBS11001 后，异源性生产异源性异源性生产在源自 S. lividans K4-114 的工程化 S. lividans SB11002 菌株中得到了成功证明。然而，在类似的发酵条件下，工程菌株的iso-MGS滴度明显低于原生生产者——Streptomyces platensis NRRL 18993。为了避免iso-MGS滴度低的问题，并扩大这种异源系统的效用针对iso-MGS的生物合成和工程化，对发酵培养基进行了系统优化。使用单因素优化方法研究了培养基中主要成分的影响，包括碳源、有机氮源和无机氮源。其结果，蔗糖和酵母提取物被确定为最佳的碳源和有机氮源，从而优化了 iso-MGS 的生产。相反，评估的所有其他无机氮源对 iso-MGS 产生产生不同程度的抑制。最终优化的 R2YE 生产培养基产生的 iso-MGS 的滴度为 86.5 mg/L，比原始 R2YE 培养基高约 3.6 倍，比天然 S. platensis NRRL 18993 生产者高 1.5 倍。