Metabolic engineering; novel approach which guides the improvement of biological processes by identifying gene targets

Most chemicals are currently derived from fossil feedstocks. Dr Marcellin’s research is trying to shift production of these chemicals to more sustainable alternatives; by using living cells as cell factories we are converting bio-based feedstocks into chemicals and fuels. Our research goes beyond conventional sugars as fermentation feedstocks: we are using gasified waste as a more sustainable alternative. Gas fermentation not only does not compete with arable land or the food chain but is also readily available at a low cost. To produce value added chemicals however, cells need to be metabolically engineered and new processes need to be developed and optimized.

To achieve this goal, we use systems metabolic engineering, a powerful novel approach which guides the improvement of biological processes by identifying gene targets for engineering. Using a knowledge driven approach that takes advantage of the growth in high throughput omics (genomics, transcriptomics, metabolomics proteomics and phosphoproteomics) coupled with mathematical models, we can understand, predict, and optimize the properties and behaviour of cells (e.g. identification of gene targets for knock out/up-regulation). The combination of these experimental and computational tools can also be used to drive yields and productivities close to capacity. Generally, these improvements require various iterative rounds. Thus, the models are constantly refined and validated using biological (omics) data leading to further rounds of metabolic engineering, which in the end, drive cells close to the maximum theoretical yield.

In collaboration with leaders in the industry, we are currently applying systems metabolic engineering to produce propionic acid, enhance clostridial vaccine yields and to increase the production scope of gas fermenting bacteria.

Key publications

Valgepea K, de Souza Pinto Lemgruber R, Meaghan K, Palfreyman RW,  Abdalla T, Heijstrac BJ, Behrendorff JB, Tappel R, Köpke M, Simpson SD, Nielsen LK, Marcellin E (2016) Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens. Cell Systems 4 (5), 505-515.

Valgepea K, Loi K, Behrendorff JB, de SP Lemgruber R, Plan M, Hodson MP, Köpke M, Nielsen LK, Marcellin E (2016) Arginine deiminase pathway provides ATP and boosts growth of the gas-fermenting acetogen Clostridium autoethanogenum Metabolic Engineering 41, 202-211.

Marcellin E, Behrendorff JB, Nagaraju S, DeTissera S, Segovia S, Palfreyman R, Daniell J, Licona-Cassani C, Quek L, Speight R, Hodson M, Simpson S, Mitchell W, Köpke M, Nielsen LK. (2016). Low carbon fuels and commodity chemicals from waste gases–Systematic approach to understand energy metabolism in a model acetogen. Green Chemistry 18 (10), 3020-3028

Marcellin E, Licona C, Mercer TR, Palfreyman RW, Nielsen LK. (2013) Re-annotation of the Saccharopolyspora erythraea genome using a systems biology approach. BMC Genomics 14 (1) 699.

Marcellin E, Chen WY, Nielsen, LK. (2010). Understanding plasmid effect on hyaluronic acid molecular weight produced by Streptococcus equi subsp. Zooepidemicus. Metabolic Engineering 12 1: 62-69.