Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea
Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea
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DOI：
10.1007/s10295-006-0094-3
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Weber, J. Mark
中科院分区：
文献类型：
--
作者：
Reeves, Andrew R.;Brikun, Igor A.;Weber, J. Mark
在红糖多孢菌的碳水化合物发酵中，甲基丙二酰辅酶 A 变位酶 (MCM) 基因 mutB 的极性敲除可将红霉素产量平均提高 126%（在 0.95 置信区间的 102-153% 范围内）。在基于油的发酵中，野生型菌株的红霉素产量平均比基于碳水化合物的发酵高 184%（141-236%，0.95 CI），而 mutB 中相同的极性敲除令人惊讶地使红霉素产量减少了 66%（5376%，0.95 CI）。提出了一种代谢模型，其中在基于碳水化合物的发酵中，MCM充当甲基丙二酰辅酶A代谢物库的排水管，而在基于油的发酵中，MCM以相反的方向起作用以填充甲基丙二酰辅酶A库。因此，该模型部分解释了众所周知的红霉素生产油基工艺改进如何在生化水平上进行；此外，它还说明了 mutB 红霉素菌株改良突变如何在基于碳水化合物的发酵中在基因水平上发挥作用。
In carbohydrate-based fermentations of Saccharopolyspora erythraea, a polar knockout of the methylmalonyl-CoA mutase (MCM) gene, mutB, improved erythromycin production an average of 126% (within the range of 102-153% for a 0.95 confidence interval). In oil-based fermentations, where erythromycin production by the wild-type strain averages 184% higher (141-236%, 0.95 CI) than in carbohydrate-based fermentations, the same polar knockout in mutB surprisingly reduced erythromycin production by 66% (5376%, 0.95 CI). A metabolic model is proposed where in carbohydrate-based fermentations MCM acts as a drain on the methylmalonyl-CoA metabolite pool, and in oil-based fermentations, MCM acts in the reverse direction to fill the methylmalonyl-CoA pool. Therefore, the model explains, in part, how the well-known oil-based process improvement for erythromycin production operates at the biochemical level; furthermore, it illustrates how the mutB erythromycin strain improvement mutation operates at the genetic level in carbohydrate-based fermentations.