Activation and enhancement of Fredericamycin A production in deepsea-derived Streptomyces somaliensis SCSIO ZH66 by using ribosome engineering and response surface methodology

• DOI: 10.1186/s12934-015-0244-2
• Publication Date: 2015-05-08T13:01:18Z
• Authors: Yonghe Zhang; Huiming Huang; Shanshan Xu; Bo Wang; Jianhua Ju; Huarong Tan; Wenli Li
• Keywords: Strain (injury); Synthetic Biology; Gene cluster

Marine microorganisms are an important source of new drug leads. However, the discovery and sustainable production these compounds often hampered due to unavailable expression cryptic biosynthetic gene clusters or limited titer. Ribosome engineering response surface methodology (RSM) integrated strategy was developed in this study activate cluster deepsea-derived Streptomyces somaliensis SCSIO ZH66, subsequently isolation, structural analysis, yield enhancement activated compound, anticancer lead Fredericamycin A (FDM A), were performed. In order discover novel natural products from marine strains by genome mining strategy, S. ZH66 subject ribosome clusters. resistant strain ZH66-RIF1 thereby obtained with 300 μg/mL rifampicin, which accumulated a brown pigment cytotoxicity on MS plate while absent wild type strain. After screening fermentation conditions, compound purified identified be FDM A, indicating that activation taken place ZH66-RIF1, then it ascribed mutation R444H β subunit RNA polymerase. To further improve efficiently, nine medium components examined for their significance Plackett–Burman design Box-Behnken design. The optimum composition achieved RSM under titer reached 679.5 ± 15.8 mg/L after 7 days fermentation, representing 3-fold increase compared original medium. terms short time low-cost medium, would ideal alternative production. Our results hasten efforts development as candidate. Moreover, is effective, fast efficient; applicable other strains.