What is bioproduction?

Bioproduction is a research field which covers the whole process of that living organisms produce various types of products, such as materials for food, pharmaceutical products, biofuels, biological tools, bio-plastics. Extraction and purification processes are needed in certain types of products, while the living organisms themselves are often used as they are. Breeding and production process management are the key points in the research field.

Why bioproduction is important for us?

The bioproducts mentioned above are made from low cost materials, such as light, CO2, inorganic salts, starch, and feed crops. Certain products can be produced by bioproduction with far lower cost than by chemical synthesis. Not only cost effective, bioproduction is regarded as environment friendly and more sustainable. Here we propose research strategies to promote the bioproduction research, particularly to build up the guiding principle for effective breeding and production process management in a systematic way. As the research background, current issues and relevant industries vary among the types of organisms used, our proposals are divided into three parts. The first one argues the bioproduction by microorganisms and cultured cells, the second is for fishery and animal husbandry, and the third part refers to agriculture (mainly plants).

Background and present state

Microorganisms and cultured cells deliver bioproducts via a series of bioreaction through their metabolic pathway. For the effective bioproduction, desired metabolic pathways have to be designed and implemented in the cells; however, the manipulation of metabolic pathways is not trivial. The number of possible metabolic pathways can be enormous; our current computing capacity is not enough to simulate the functions and behaviour of bio-molecules and bio-reaction in the cells. Thus, current bioproduction design mainly relies on the manipulation of natural metabolic pathways; numerous numbers of transgenic cell lines which carry various types of manipulated metabolic pathways are created and multiple combinations of them are tested. Vast amount of data is acquired from such experiments and analysed via advanced statistics and/or machine learning, leading to pick up the most possibly successful strains. Iterative process of such try and error (design-build-test-learn-redesign) is necessary to establish the successful strain for effective bioproduction.

Current Issues

As current bioproduction design relies on theory of chance to obtain the successful one, even if a certain bio-molecule or a bioproduction pathway works in certain cells/strains, it is unpredictable whether the molecule or the pathway works in other organisms or strains. Furthermore, when the system failed to work in other organisms/cells, it is neither possible to detect the causal factors nor to plan the bypass route to avoid the problematic processes. Notably, it is currently impossible to de novo design of substances having functions which do not exist in nature.

Proposed research strategy

As we have defined that current issues are caused by the lack of guiding principle for the bioproduction design, we propose that it is essential to build the effective methodology to design bioproduction pathways, with uncovering the rules of life. We have identified two types of major design failures: the failure in bio-components, for example, enzymes in the introduced pathways fail to express/work properly, and the disruption/conflict in metabolic pathways in the microorganisms/cultured cells. Here we propose following two strategies to tackle the issues.

• Theme 1: Efficient & effective design of bio-component used in the bioproduction process.

  The genetic information of the introduced bio-component, such as the DNA code of an enzyme has to be correctly copied onto mRNA, then the relevant amino acids should be properly assembled and the whole protein should be folded, transported appropriately to work effectively. As everything has already been optimised in the naturally occurring bioprocess, it is very challenging to find out the focal point in the artificially introduced/manipulated bioprocess. To uncover such overlooked principle and constraint, in which nature has already optimised, provides both deeper understanding of the central dogma in molecular biology and transformative innovation in the bioproduction.

• Theme 2: Efficient & effective design of metabolic pathway in the bioproduction process.

  Shortage of cellular resource caused by the introduced/manipulated metabolic pathway is one of the common causes of the failure in bioproduction design. In addition to such cellular capacity, the robustness of the metabolic pathway at the whole cell level could be affected by the manipulation. To clarify the cellular capacity and fluctuations in metabolism in the manipulated cells would facilitate the essential conditions for the introduced/manipulated metabolic pathways to work properly. To estimate and eliminate the possible defective metabolic pathways at the point of design could provide efficient, accurate, and effective bioproduction design, including the efficient scale up to industry level production.

In addition to above described two research strategies, we would emphasise that it is inevitable to upgrade and strengthen the research environment and its foundation, to conduct such transformative research. As described above, bioproduction with microorganisms and cultured cells covers wide range of topics in cell biology, such as nucleic acids, proteins, metabolic pathways, cellular capacity to conduct all the biological events. All these components are tightly linked, thus have to be analysed and understood in a cross-linked and multi-level manner. Various types of analytical instruments and technologies are needed to meet such advanced research objectives; however, nowadays all the instrument/technology costs extremely high, which is not affordable for single laboratory. Considering such circumstances, the most feasible strategy for the systematic promotion of the research and application in the industry could be: to establish an integrative research centre for basic and translational research. The research centre should provide following three nexus functions: (1) the research head quarter to manage whole research progress, (2) integrated research facility (providing a series of advanced analytical instruments and services) for data acquisition and analysis, and (3) pilot plants to test whether the designed system works at smaller scale.

As the data size gains and gains nowadays, such integrative research centre could contribute for both the promotion of corporation with informatics and career development for researchers to be fit in the inter- and cross-disciplinary research.