Moreira Jean Vinícius, Silva Seforah Carolina Marques, Cremasco Marco Aurélio
University of Campinas, School of Chemical Engineering, Department of Process Engineering, Campinas, Brazil.
Biotechnol Rep (Amst). 2020 Feb 20;26:e00440. doi: 10.1016/j.btre.2020.e00440. eCollection 2020 Jun.
Tacrolimus is an immunosuppressant produced by several species, widely used in transplantolgy and dermatology. In this report, attempts have been made to enhance tacrolimus productivity by altering the primary carbon source on culture media. In order to better understand the effects of glucose and maltose on tacrolimus biosynthesis, different carbon contents of these sugars were evaluated in the culture media, thus altering the carbon:nitrogen ratio. The highest specific production achieved on this report was 10.46 mg/g at a carbon:nitrogen ratio of 8.7:1.0 and maltose as carbon source. Using glucose as primary carbon source, the highest specific production achieved was 9.06 mg/g at a carbon:nitrogen ratio of 8.5:1.0. The range of carbon:nitrogen ratios evaluated for each sugar presented distinct behaviors. Glucose containing-media exhibited an initial linear downward trend, by the other hand, maltose containing-media exhibited an increasing tendency. Both glucose and maltose presented the highest specific production at 3 % of carbon source on media. Media containing more than 3 % of carbon content exerted carbon catabolite repression. The range of carbon:nitogen ratios evaluated presented an increasing tendency on tacrolimus biosynthesis up to 3 % of glucose or maltose in the media, both carbon sources exerted the phenomenon of carbon catabolite repression with more than 3 % of carbon source on the media.
他克莫司是由多种物种产生的一种免疫抑制剂,广泛应用于移植学和皮肤病学领域。在本报告中,已尝试通过改变培养基中的主要碳源来提高他克莫司的产量。为了更好地理解葡萄糖和麦芽糖对他克莫司生物合成的影响,在培养基中评估了这些糖类的不同碳含量,从而改变碳氮比。本报告中实现的最高比产量是在碳氮比为8.7:1.0且以麦芽糖作为碳源时达到的10.46毫克/克。以葡萄糖作为主要碳源时,在碳氮比为8.5:1.0时实现的最高比产量为9.06毫克/克。针对每种糖类评估的碳氮比范围呈现出不同的行为。含葡萄糖的培养基呈现出初始线性下降趋势,另一方面,含麦芽糖的培养基呈现出上升趋势。葡萄糖和麦芽糖在培养基中碳源含量为3%时均呈现出最高比产量。碳含量超过3%的培养基会产生碳分解代谢物阻遏。评估的碳氮比范围在培养基中葡萄糖或麦芽糖含量达到3%之前对他克莫司生物合成呈现出上升趋势,当培养基中碳源含量超过3%时,两种碳源都会产生碳分解代谢物阻遏现象。