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히알루론산 생산성 향상을 위한 Streptococcus zooepidemicus 균주 개량 및 발효조 배양공정 최적화

Strain Improvement and Bioprocess Optimization for Enhanced Production of Haluronic Acid(HA) in Bioreactor Cultures of Streptococcus zooepidemicus

Microbiology and Biotechnology Letters 2020년 48권 3호 p.344 ~ 357
김수연, 전계택,
소속 상세정보
김수연 ( Kim Soo-Yeon ) - Kangwon National University College of Biomedical Sciences
전계택 ( Chun Gie-Taek ) - Kangwon National University College of Biomedical Sciences

Abstract


Strain improvement and bioprocess development were undertaken to enhance hyaluronic acid(HA) production by Streptococcus zooepidemicus cells. Using a high-yielding mutant strain, statistical medium optimization was carried out in shake flask cultures, resulting in 52% increase in HA production (5.38 g/l) at the optimal medium composition relative to the parallel control cultures. For sufficient supply of dissolved oxygen (DO), which turned out to be crucial for enhanced production of HA, agitation system and speed were intensively investigated in 5 L bioreactor cultures. Increase in oxygen mass transfer coefficient (kLa) through increment of agitation speed (rpm) and 35% expansion of diameter of the newly-designed impellers showed significantly positive effects on HA production. By installing an expanded Rushton-turbine impeller for efficient break-down of sparged air, and an extended marine impeller above the Rushton-turbine impeller for efficient mixing of the air-born viscous fermentation broth, maximum amount of HA (9.79 g/l) was obtained at 450 rpm, 1.8 times higher level than that of the corresponding flask culture. Subsequently, the possibility of bioprocess scale-up to a 50 L bioreactor was investigated. Despite almost identical maximum HA production (9.11 vs 9.25 g/l), the average HA volumetric productivity (rp) of the 50 L culture turned out only 74% compared to the corresponding 5 L culture during the exponential phase, possibly caused by shear damages imposed on the producing cells at the high stirring in the 50 L culture. The scale-up process could be successfully achieved if a scale-up criterion of constant oxygen mass transfer coefficient (kLa) is applied to the 50 L pilot-scale bioreactor system.

키워드

Hyaluronic acid; Streptococcus zooepidemicus; statistical medium optimization; agitation system; scale-up of bioreactor cultures

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