To improve the production of secondary metabolites by alternation of the carbon metabolic flux, two types of deletion mutants of the central metabolic pathway, the Embden–Meyerhof (EM) or pentose phosphate (PP) pathway, in the genetically engineered Streptomyces avermitilis were constructed. Double-deletion mutants of phosphofructokinase (ΔpfkA1ΔpfkA3) in the EM pathway carrying a gene cluster for chloramphenicol biosynthesis markedly increased chloramphenicol production synthesized through the shikimate pathway. Although the ΔpfkA1ΔpfkA3 double-deletion mutant grew more slowly, its specific productivity of chloramphenicol (per dry cell weight) was 2.0-fold higher than that of the engineered S. avermitilis strain. However, the productivity of chloramphenicol was lower by the double-deletion mutant of transaldolase in the PP pathway, which supplies the precursor of the shikimate pathway. A carbon-flux analysis of the EM and PP pathways using [1–¹³C] glucose revealed that carbon flux in the ΔpfkA1ΔpfkA3 double-deletion mutant increased through the PP pathway, which enhanced the production of chloramphenicol. These results suggest that a metabolic modification approach has the potential to increase the titers and yields of valuable secondary metabolites.

为了通过改变碳代谢通量来提高次级代谢产物的产生，在基因工程改造的阿维链霉菌中构建了两种类型的中央代谢途径的缺失突变体，即Embden-Meyerhof（EM）或戊糖磷酸（PP）途径。EM途径中带有果糖生物合成基因簇的磷酸果糖激酶（ΔpfkA1ΔpfkA3）的双缺失突变体显着增加了通过synthesized草酸酯途径合成的氯霉素的产量。尽管ΔpfkA1ΔpfkA3双缺失突变体的生长较慢，但其氯霉素的比生产率（每干细胞重量）比工程改造的阿维链霉菌高2.0倍。应变。然而，通过PP途径中的转醛缩酶的双缺失突变体，氯霉素的生产率较低，其提供了iki草酸酯途径的前体。使用EM和PP途径的碳通量分析[1- ¹³ C]葡萄糖揭示了在该碳通量ΔpfkA1ΔpfkA3双缺失突变体通过PP途径，这提高了生产氯霉素增加。这些结果表明，代谢修饰方法有可能增加有价值的次级代谢产物的效价和产量。