Carteni Fabrizio, Occhicone Alessio, Giannino Francesco, Vincenot Christian E, de Alteriis Elisabetta, Palomba Emanuela, Mazzoleni Stefano
Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy.
Department of Engineering, University of Naples Parthenope, Naples, Italy.
Front Microbiol. 2020 Sep 30;11:521368. doi: 10.3389/fmicb.2020.521368. eCollection 2020.
The metabolic shift between respiration and fermentation at high glucose concentration is a widespread phenomenon in microbial world, and it is relevant for the biotechnological exploitation of microbial cell factories, affecting the achievement of high-cell-densities in bioreactors. Starting from a model already developed for the yeast , based on the System Dynamics approach, a general process-based model for two prokaryotic species of biotechnological interest, such as and , is proposed. The model is based on the main assumption that glycolytic intermediates act as central catabolic hub regulating the shift between respiratory and fermentative pathways. Furthermore, the description of a mixed fermentation with secondary by-products, characteristic of bacterial metabolism, is explicitly considered. The model also represents the inhibitory effect on growth and metabolism of self-produced toxic compounds relevant in assessing the late phases of high-cell density culture. Model simulations reproduced data from experiments reported in the literature with different strains of non-recombinant and recombinant and cultured in both batch and fed-batch reactors. The proposed model, based on simple biological assumptions, is able to describe the main dynamics of two microbial species of relevant biotechnological interest. It demonstrates that a reductionist System Dynamics approach to formulate simplified macro-kinetic models can provide a robust representation of cell growth and accumulation in the medium of fermentation by-products.
在高葡萄糖浓度下，微生物呼吸与发酵之间的代谢转变是微生物界普遍存在的现象，这与微生物细胞工厂的生物技术开发相关，影响生物反应器中高细胞密度的实现。从基于系统动力学方法已为酵母开发的模型出发，提出了一个针对两种具有生物技术应用价值的原核生物（如[具体物种1]和[具体物种2]）的基于过程的通用模型。该模型基于这样一个主要假设：糖酵解中间产物作为核心分解代谢枢纽，调节呼吸途径和发酵途径之间的转变。此外，还明确考虑了具有细菌代谢特征的伴有二次副产物的混合发酵的描述。该模型还体现了自产生的有毒化合物对生长和代谢的抑制作用，这在评估高细胞密度培养后期时具有重要意义。模型模拟重现了文献中报道的不同非重组和重组[具体物种1]及[具体物种2]菌株在分批和补料分批反应器中培养的实验数据。所提出的模型基于简单的生物学假设，能够描述两种具有重要生物技术应用价值的微生物物种的主要动态。它表明，采用简化论的系统动力学方法来构建简化的宏观动力学模型，可以为发酵副产物在培养基中的细胞生长和积累提供有力的表征。
