Fermentation Of Engineered Strain Streptomyces Focculus CGMCC4.1223ΔstnB1for Lavendamycin Production

Lavendamycin methyl ester (LME) is a derivative of a highlyfunctionalized aminoquinone alkaloid lavendamycin and could be used asscaffold for novel anticancer agent development. This work demonstratedLME production by cultivation of an engineered strain of StreptomycesfocculusCGMCC4.1223ΔstnB1whilethewildtypestraindidnotproduce.Through fermentation optimization, the LME production in ΔstnB1straincould achieve66.1mg/L at10g/L glucose,30g/L soybean powdercultivated at30°C with1%inoculation volume, increased15foldscompared with original condition. To further enhance the production, theeffect of shear stress and oxygen supply on ΔstnB1strain fermentation wasinvestigated in detail. In flask culture, when the shaking speed increasedfrom150rpm to220rpm, the mycelium was altered from large pellet tofilamentous hypha and the LME production was almost doubled, while nosignificant differences were observed among varied filling volumes, whichimplied a crucial role of shear stress in the morphology and LMEproduction. To confirm this suggestion, experiments with agitation speedranging from400rpm to1000rpm at a fixed aeration rate of1.0vvm were conducted in a stirred tank bioreactor. It was found that the morphologybecame more hairy with reduced pellet size and the LME production wasenhanced to three folds when the agitation speed increased from400to800rpm, and the highest LME production of159.6mg/L was obtained at800rpm. Further experiments by varying initial KLa value at the same agitationspeed indicated that oxygen supply only slightly affected the physiologicalstatus of ΔstnB1strain. Altogether, shear stress was identified as a majorfactor affecting the cell morphology and LME production. The work wouldbe helpful to the production of LME and other secondary metabolites byfilamentous microorganism cultivation.