Microbial superhost strains should provide an ideal platform for the efficient homologous or heterologous phenotypic expression of biosynthetic gene clusters (BGCs) of new and novel bioactive molecules. Our aim in the current study was to perform a comparative study at the bioprocess and metabolite levels of the previously designed superhost strain Streptomyces coelicolor M1152 and its derivative strain S. coelicolor M1581 heterologously expressing chloramphenicol BGC. Parent strain M1152 was characterized by a higher specific growth rate, specific CO₂ evolution rate, and a higher specific l-glutamate consumption rate as compared with M1581. Intracellular primary central metabolites (nucleoside/sugar phosphates, amino acids, organic acids, and CoAs) were quantified using four targeted LC-MS/MS-based methods. The metabolite pathways in the nonantibiotic producing S. coelicolor host strain were flooded with carbon from both carbon sources, whereas in antibiotic-producing strain, the carbon of l-glutamate seems to be draining out through excreting synthesized antibiotic. The ¹³C-isotope-labeling experiments revealed the bidirectionality in the glycolytic pathway and reversibility in the non-oxidative part of PPP even with continuous uptake of d-glucose. The change in the primary metabolites due to the insertion of BGC disclosed a clear linkage between the primary and secondary metabolites.

中文翻译：

---

超宿主菌株天蓝色链霉菌M1152及其衍生物M1581异源表达氯霉素生物合成基因簇的生物过程和代谢物水平的比较研究

微生物超宿主菌株应为新型和新型生物活性分子的生物合成基因簇 (BGC) 的有效同源或异源表型表达提供理想平台。我们目前研究的目的是对先前设计的超宿主菌株天蓝色链霉菌M1152 及其衍生菌株天蓝色链霉菌M1581 异源表达氯霉素 BGC的生物过程和代谢物水平进行比较研究。亲本菌株M1152具有较高的比生长速率、比 CO ₂释放速率和较高的比生长速率。-谷氨酸消耗率与M1581相比。使用四种基于 LC-MS/MS 的靶向方法对细胞内初级中心代谢物（核苷/糖磷酸盐、氨基酸、有机酸和 CoA）进行量化。在不产生抗生素的天蓝色链球菌宿主菌株中的代谢物途径充满了来自两种碳源的碳，而在产生抗生素的菌株中，L-谷氨酸的碳似乎通过排泄合成的抗生素排出。¹³ C-同位素标记实验揭示了糖酵解途径的双向性和 PPP 非氧化部分的可逆性，即使连续摄取d-葡萄糖。由于 BGC 的插入，初级代谢物的变化揭示了初级和次级代谢物之间的明确联系。