State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Enzyme Microb Technol. 2012 May 10;50(6-7):318-24. doi: 10.1016/j.enzmictec.2012.03.001. Epub 2012 Mar 17.
Oxytetracycline (OTC) is a widely used antibiotic, which is commercially produced by Streptomyces rimosus. The type II minimal polyketide synthases (minimal PKS) genes of the oxytetracycline biosynthesis cluster in S. rimosus, consisting of oxyA, oxyB and oxyC, are involved in catalyzing 19-C chain building by the condensation of eight malonyl-CoA groups to form the starting polyketide. This study aimed to investigate the effects of overexpression of the minimal PKS gene in a model S. rimosus strain (M4018) and in an industrial overproducer (SR16) by introduction of a second copy of the gene into the chromosome. Increased levels of oxyA, oxyB and oxyC gene transcription were monitored using reverse transcription quantitative real-time PCR. Overexpression of the minimal PKS gene elicited retardation of cell growth and a significant improvement in OTC production in corresponding mutants (approximately 51.2% and 32.9% in M4018 and SR16 mutants respectively). These data indicate that the minimal PKS plays an important role in carbon flux redirection from cell growth pathways to OTC biosynthesis pathways.
土霉素（OTC）是一种广泛使用的抗生素，由链霉菌（Streptomyces rimosus）商业生产。土霉素生物合成簇中的 II 型最小聚酮合酶（minimal PKS）基因，包括 oxyA、oxyB 和 oxyC，参与催化由八个丙二酰辅酶 A 缩合形成起始聚酮的 19-C 链构建。本研究旨在通过将基因的第二个拷贝引入染色体，研究最小 PKS 基因在模型链霉菌（M4018）和工业高产菌（SR16）中的过表达对其的影响。使用反转录定量实时 PCR 监测最小 PKS 基因转录水平的增加。最小 PKS 基因的过表达导致细胞生长延迟，相应突变体中 OTC 产量显著提高（在 M4018 和 SR16 突变体中分别约为 51.2%和 32.9%）。这些数据表明，最小 PKS 在将碳通量从细胞生长途径重新导向 OTC 生物合成途径方面发挥重要作用。
