The difficulty of scaling up in pilot testing lies in the extreme complexity of living systems!
However, when the innovative achievements of biomanufacturing are transformed into industrialization, they face the obstacle of a "gap" in pilot testing.
Professor Zhuang Yingping, Dean of the School of Bioengineering at East China University of Science and Technology, has been deeply involved in this field for decades. She has clearly outlined the development trajectory and industrial pattern of biomanufacturing.
1、 The current pattern of biomanufacturing
Professor Zhuang Yingping divided the development of industrial biomanufacturing into four stages: from traditional solid fermentation in ancient brewing and vinegar production, to anaerobic fermentation of primary metabolites and liquid aerobic fermentation of secondary metabolites.
The fourth stage, centered around synthetic biology and gene editing, can help address major needs such as food security, dual carbon targets, and disease treatment, such as artificial organs and cell therapy.
After multiple stages of development, biomanufacturing has formed an industrial pattern of "three parts of the world":
Green biomanufacturing (agriculture): covering gene edited crops, biopesticides, agricultural microorganisms, etc., to support the green and efficient development of agriculture;
White bio manufacturing (industrial): including bioenergy (ethanol, hydrogen), biodegradable biomaterials (PLA, PHA), industrial enzyme preparations, etc., replacing traditional high pollution chemical production;
Red biomanufacturing (pharmaceuticals): involving recombinant protein drugs, nucleic acid drugs, vaccines, artificial organs, etc., it is the core driving force of biomedical innovation.
The core advantage of biomanufacturing lies in the 'sustainable efficiency revolution'.
Taking cosmetic raw materials as an example, vitamin B5 achieves industrialization through metabolic pathway optimization and fermentation process improvement, and is closer to natural sources and easily absorbed by the skin;
Through process optimization, the fermentation yield of hyaluronic acid reached 28.7g/L, freeing itself from the limitations of animal tissue extraction.
2、 What is the problem? Trial 'Gap'
From laboratory results to industrial mass production, pilot testing is a crucial yet challenging step.
Professor Zhuang Yingping pointed out that the root of the problem lies in the extreme complexity of living systems.
Intracellular 'cellular factories' are difficult to regulate: genes and metabolic networks are intertwined within the cell, and material and energy flows are complex.
Difficulty adapting to the extracellular "reactor environment": There are "gradient fields" of nutrition, temperature, and oxygen in large reactors, and subtle differences in the layout of stirring blades and baffles may cause production efficiency fluctuations of over 10%.
At the same time, microorganisms have different physiological states during different stages of fermentation, and environmental parameters need to be dynamically adjusted, otherwise they will deviate from the optimal metabolic state.
3、 What should we do? Multi scale regulation+intelligent technology
Professor Zhuang Yingping proposed a solution based on biological process engineering and combined with intelligent technology to address the challenges in pilot testing
Multi scale collaborative regulation: Based on the "gene cell reactor" multi-scale model, select high-performance bacterial strains (gene scale), optimize processes to improve metabolic efficiency (cell scale), improve reactor structure through fluid dynamics simulation (reactor scale), and adapt each link;
Intelligent technology empowerment: Real time monitoring of cell metabolism through online Raman and infrared sensors, prediction of parameter effects using data models, and combined with adaptive control to achieve "autonomous decision-making", reducing trial and error costs and improving pilot stability.
