使用DNA芯片和利用反向工程改进工业菌株

细履平沙

Reverse engineering of industrial pharmaceutical-producing actinomycete strains using DNA microarrays

细履平沙

abstract:
Transcript levels in production cultures of wildtype and classically improved strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces fradiae were monitored using microarrays of the sequenced actinomycete S. coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics erythromycin and tylosin, respectively, and the
classically improved strains contain unknown overproduction mutations. The Sac. erythraea overproducer was found to express the entire 56-kb erythromycin gene cluster several days longer than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while they expressed several tens of other S. fradiae genes and S. coelicolor homologs differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor isobutyryl-CoA mutase homolog icmA. These observations indicated that overproduction mechanisms in classically improved strains can affect both the timing and rate of antibiotic synthesis, and alter the regulation of antibiotic biosynthetic enzymes and enzymes involved in precursor metabolism.
细履平沙译：
摘要。
本文分别使用编码了 S. coelicolor. Sac. erythraea和S. fradiae菌株合成聚酮抗生素红霉素和泰乐菌素的基因芯片对野生菌和传统改良的生产菌株（ 放线菌Saccharopolyspora erythraea and Streptomyces fradiae ）进行了对比。发现生产菌株包含一些未知的变异。红霉素生产菌Sac. erythraea能够表达一个完整的56KB的红霉素基因簇，表达能力比野生菌长几天。相应的，S. fradiae野生型和生产菌株表达了相近的85KB泰乐菌素合成基因簇，然而表达的其它几十个 S. fradiae和S. coelicolor 基因有不同的同源性。这些基因包括乙酰coA脱氢酶aco和异丁酰coA变异酶icmA。
这些结果表明：由传统方法改造的生产菌株能够影响抗生素合成的时间和速率，而且改变了抗生素合成酶及前体合成相关酶的调节。

juanwenyy

good

yulei0229

称为逆代谢工程更好一些

系统生物学是发展方向，
但真正从系统生物学得到工程菌，各项指标达到目前生产菌的要求，路还很遥远。

只能说，系统生物学让我们对高产代谢产物的机理了解的更多了一些。