An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain.
An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain.
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DOI：
10.1007/s00253-011-3650-3
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发表时间：
2012-02
影响因子：
5
通讯作者：
Wesley, Roy K.
中科院分区：
文献类型：
--
作者：
Weber, J. Mark;Cernota, William H.;Gonzalez, Melissa C.;Leach, Benjamin I.;Reeves, Andrew R.;Wesley, Roy K.
红糖多孢菌 mutB 敲除菌株 FL2281 在甲基丙二酰辅酶 A 变位酶反应中具有阻断作用，被发现在油基发酵培养基中携带甲基丙二酸二乙酯响应 (Dmr) 表型。当油基培养基中添加 15 mM 水平的该溶剂时，Dmr 表型能够将红霉素 A（红霉素）产量提高 250% – 300%。较低浓度的溶剂刺激的红霉素产量相应减少，而较高浓度则没有额外的好处。尽管 mutB 菌株在表型上是低水平的红霉素生产者，但补充甲基丙二酸二乙酯使其比野生型（对照）菌株（不显示 Dmr 表型的菌株）多产生 30% 的红霉素。 Dmr 表型代表了一类新的菌株改良表型。提出了解释 Dmr 表型生化机制的理论。发现与 mutB 敲除相关的其他表型是生长缺陷和色素沉着过度，这两种表型都通过暴露于甲基丙二酸二乙酯恢复正常。此外，在甲基丙二酸二乙酯存在的情况下，mutB 发酵不会显着代谢大豆油。最后，提出了一种分离具有 Dmr 表型的其他突变体的新方法。
The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250 – 300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild type (control) strain--a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype.
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影响因子：
--
作者：
Zhang, Haoran;Wang, Yong;Pfeifer, Blaine A.
通讯作者：
Pfeifer, Blaine A.
DOI：
10.1007/s10295-004-0154-5
发表时间：
2004-08-01
影响因子：
3.4
作者：
Brikun, IA;Reeves, AR;Weber, JM
通讯作者：
Weber, JM
影响因子：
2.9
作者：
Lombó, F;Pfeifer, B;Khosla, C
通讯作者：
Khosla, C
DOI：
10.1007/s10295-006-0094-3
发表时间：
2006-07-01
影响因子：
3.4
作者：
Reeves, Andrew R.;Brikun, Igor A.;Weber, J. Mark
通讯作者：
Weber, J. Mark
影响因子：
3.2
作者：
Kwan, David H.;Tosin, Manuela;Leadlay, Peter F.
通讯作者：
Leadlay, Peter F.