New opportunities and challenges for hybrid data and model driven bioprocess optimization and scale-up / 生物工程学报

Currently, biomanufacturing technology and industry are receiving worldwide attention. However, there are still great challenges on bioprocess optimization and scale-up, including: lacing the process detection methods, which makes it difficult to meet the requirement of monitoring of key indicators and parameters; poor understanding of cell metabolism, which arouses problems to rationally achieve process optimization and regulation; the reactor environment is very different across the scales, resulting in low efficiency of stepwise scale-up. Considering the above key issues that need to be resolved, here we summarize the key technological innovations of the whole chain of fermentation process, i.e., real-time detection-dynamic regulation-rational scale-up, through case analysis. In the future, bioprocess design will be guided by a full lifecycle in-silico model integrating cellular physiology (spatiotemporal multiscale metabolic models) and fluid dynamics (CFD models). This will promote computer-aided design and development, accelerate the realization of large-scale intelligent production and serve to open a new era of green biomanufacturing.

Construction and verification of Lactococcus lactis NZ9000 genome-scale metabolic model / 生物工程学报

With the advent of the post-genomic era, metabolic engineering of microorganisms plays an increasingly important role in industrial production. The genome-scale metabolic model (GSMM) integrates all known metabolic information in the organism to provide an optimal platform for global understanding of the metabolic state of the organism and rational guidance for metabolic engineering. As a model strain, Lactococcus lactis NZ9000 plays an important role in industrial fermentation, but there is still no specific genome-scale metabolic model for it. Based on genomic function annotation and comparative genomics, we constructed the first genome-scale metabolic model iWK557 of L. lactis NZ9000, which contains 557 genes, 668 metabolites, and 840 reactions, and further verified at both qualitative and quantitative levels, to provide a good tool for rationally guiding metabolic engineering.

Application of metabolic network model to analyze intracellular metabolism of industrial microorganisms / 生物工程学报

To quickly and efficiently understand the intracellular metabolic characteristics of industrial microorganisms, and to find potential metabolic engineering targets, genome-scale metabolic network models (GSMMs) as a systems biology tool, are attracting more and more attention. We review here the 20-year history of metabolic network model, analyze the research status and development of GSMMs, summarize the methods for model construction and analysis, and emphasize the applications of metabolic network model for analyzing intracellular metabolic activity of microorganisms from cellular phenotypes, and metabolic engineering. Furthermore, we indicate future development trend of metabolic network model.

Glucose metabolism modeling of diabetes patients with different intensities of aerobic exercise: an in silico study / 生物医学工程学杂志

Exercise is vital for diabetics to improve their blood glucose level. However, the quantitative relationship between exercise modes (including types, intensity, time, etc.) and the blood glucose is still not clear. In order to answer these questions, this paper established a blood glucose metabolic model based on ordinary differential equation method. Furthermore, a silico method was adopted to study the effects of different aerobic exercise intensities (light, moderate and vigorous) on blood glucose and optimal strategies of insulin infusion for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Additionally, the universality of proposed model and insulin infusion strategies was verified based on 1 000 virtual diabetes patients' simulation. The experimental results showed that: (1) Vigorous-intensity aerobic exercise may result in hypoglycemia ( 6.11 mmol/L) period, however, its overall blood glucose risk index (BGRI) was lower. (2) Insulin dosage of the optimized strategies decreased by 50% and 84% for T1DM and T2DM when they did moderate intensity exercise. As for light intensity exercise, the dosage of insulin was almost the same as they didn't do exercise, but BGRI decreased significantly. (3) The simulations of 1 000 virtual diabetic patients manifested that the proposed model and the insulin infusion strategies had good universality. The results of this study can not only help to improve the quantitative understanding about the effects of aerobic exercise on blood glucose of diabetic patients, but also contribute to the regulation and management of blood glucose in exercise mode.