Tesche Sebastian, Rösemeier-Scheumann René, Lohr Jonas, Hanke René, Büchs Jochen, Krull Rainer
Institute of Biochemical Engineering Technische Universität Braunschweig Braunschweig Germany.
Center of Pharmaceutical Engineering (PVZ) Technische Universität Braunschweig Braunschweig Germany.
Eng Life Sci. 2019 Sep 8;19(11):781-794. doi: 10.1002/elsc.201900036. eCollection 2019 Nov.
Salt-enhanced cultivation as a morphology engineering tool for the filamentous actinomycete was evaluated in 500-mL shaking flasks (working volume 100 mL) with the aim of increasing the concentration of the pharmaceutically interesting peptide labyrinthopeptin A1. Among the inorganic salts added to a complex production medium, the addition of (NH)SO led to the highest amount of labyrinthopeptin A1 production. By using 50 mM (NH)SO, the labyrinthopeptin A1 concentration increased up to sevenfold compared to the non-supplemented control, resulting in 325 mg L labyrinthopeptin A1 after 10 days of cultivation. The performance of other ammonium- and sulfate-containing salts (e.g., NHCl, KSO) was much lower than the performance of (NH)SO. A positive correlation between the uptake of glycerol as one of the main carbon sources and nongrowth-associated labyrinthopeptin productivity was found. The change in the cell morphology of in conjunction with increased osmolality by the addition of 50 mM (NH)SO, was quantified by image analysis. always developed a heterogeneous morphology with pellets and loose mycelia present simultaneously. In contrast to the non-supplemented control, the morphology of (NH)SO-supplemented cultures was characterized by smaller and circular pellets that were more stable against disintegration in the stationary production phase.
作为丝状放线菌形态工程工具的盐强化培养在500 mL摇瓶(工作体积100 mL)中进行了评估,目的是提高具有药学意义的肽类迷宫肽A1的浓度。在添加到复合生产培养基中的无机盐中,添加(NH₄)₂SO₄导致迷宫肽A1的产量最高。使用50 mM (NH₄)₂SO₄时,与未添加的对照相比,迷宫肽A1的浓度增加了高达七倍,培养10天后产生了325 mg/L的迷宫肽A1。其他含铵和硫酸盐的盐(如NH₄Cl、K₂SO₄)的性能远低于(NH₄)₂SO₄。发现作为主要碳源之一的甘油的摄取与非生长相关的迷宫肽生产力之间存在正相关。通过图像分析对添加50 mM (NH₄)₂SO₄导致的渗透压增加时的细胞形态变化进行了量化。总是呈现出一种异质形态,同时存在菌球和松散的菌丝体。与未添加的对照相比,添加(NH₄)₂SO₄的培养物的形态特征是较小的圆形菌球,在静止生产阶段对解体更稳定。