Systems Biology of Industrial Microorganisms

Abstract

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Differential proteomic analysis highlights metabolic strategies associated with balhimycin production in Amycolatopsis balhimycina chemostat cultivations

“…Proteomics was proven useful to identify specific biochemical pathways (or parts thereof) and key enzymes to be further targeted in genetic manipulations aimed to maximize the conversion of substrates into useful end-products in microorganisms [21,22]. In this context, we have recently used a differential proteomic approach to demonstrate that balhimycin production in batch culture is associated with the upregulation of enzymes involved in the biosynthesis of antibiotic precursors, thus suggesting that the metabolic apparatus is orientated to sustain balhimycin production [23,24].…”

Integrated Approaches for Assessment of Cellular Performance in Industrially Relevant Filamentous Fungi

“…[37][38][39] In multiple rounds of strain design, genetic modification and analysis of the resulting cellular physiology have led to sequential improvement and led to filamentous fungi as highly efficient cell factories. The directed approaches of metabolic engineering have been the main strategy for tackling substrateutilization issues, improving product yield, eliminating unwanted by-products, and introducing or extending metabolic pathways.…”

“…39,[59][60][61] This section will, therefore, concentrate on genome-wide analyses and the integration of transcriptomics data with physiological characterization in submerged cultivations. An overview of selected studies is provided in Table 2.…”

XTMS: pathway design in an eXTended metabolic space

“…Synthesis of value-added molecules in chassis organisms, such as Escherichia coli and Saccharomyces cerevisiae , through heterologous pathways requires of a careful selection and optimization of each step of the biosynthesis pathway (1, 2). Successful examples of bioproduction of pharmaceutical products in microorganisms include the production of semisynthetic artemisinin (3), taxadiene (4), farnesol (5) or naringenin (6).…”