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Significance of agitation-induced shear stress on mycelium morphology and lavendamycin production by engineered Streptomyces flocculus

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Abstract

Lavendamycin methyl ester (LME) is a derivative of a highly functionalized aminoquinone alkaloid lavendamycin and could be used as a scaffold for novel anticancer agent development. This work demonstrated LME production by cultivation of an engineered strain of Streptomyces flocculus CGMCC4.1223 ΔstnB1, while the wild-type strain did not produce. To enhance its production, the effect of shear stress and oxygen supply on ΔstnB1 strain cultivation was investigated in detail. In flask culture, when the shaking speed increased from 150 to 220 rpm, the mycelium was altered from a large pellet to a filamentous hypha, and the LME production was almost doubled, while no significant differences were observed among varied filling volumes, which implied a crucial role of shear stress in the morphology and LME production. To confirm this suggestion, experiments with agitation speed ranging from 400 to 1,000 rpm at a fixed aeration rate of 1.0 vvm were conducted in a stirred tank bioreactor. It was found that the morphology became more hairy with reduced pellet size, and the LME production was enhanced threefolds when the agitation speed increased from 400 to 800 rpm. Further experiments by varying initial k L a value at the same agitation speed indicated that oxygen supply only slightly affected the physiological status of ΔstnB1 strain. Altogether, shear stress was identified as a major factor affecting the cell morphology and LME production. The work would be helpful to the production of LME and other secondary metabolites by filamentous microorganism cultivation.

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Acknowledgments

Financial support from the National Basic Research Program of China (973 program no. 2012CB721006) and the National Natural Science Foundation of China (NSFC Project No. 30821005) are gratefully acknowledged. The authors express their appreciation to the Analytical Centers of Shanghai Jiao Tong University and the School of Life Sciences & Biotechnology for spectrum analysis.

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Authors and Affiliations

  1. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China

    Xue Xia, Shuangjun Lin, Xiao-Xia Xia, Feng-Song Cong & Jian-Jiang Zhong

  2. Laboratory of Molecular Biochemical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China

    Xue Xia, Xiao-Xia Xia & Jian-Jiang Zhong

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  1. Xue Xia
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  2. Shuangjun Lin
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Correspondence to Jian-Jiang Zhong.

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Xia, X., Lin, S., Xia, XX. et al. Significance of agitation-induced shear stress on mycelium morphology and lavendamycin production by engineered Streptomyces flocculus . Appl Microbiol Biotechnol 98, 4399–4407 (2014). https://doi.org/10.1007/s00253-014-5555-4

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  • DOI: https://doi.org/10.1007/s00253-014-5555-4

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