Synthetic data generation for the optimization of strains in metabolic engineering using latent space representations derived from a Conditional Variational Autoencoder

This study investigates the application of generative models for synthetic data generation in pathway optimization experiments within the field of metabolic engineering. Conditional Variational Autoencoders (CVAEs) use neural networks and latent variable distributions to generate new, plausible data samples. We adapt this model by conditioning...

Living With Data

The research and design hypothesize how data centers can complement the urban environment rather than make a negative impact, both environmentally and spatially. Data centers consume and produce a variety of valuable flows, ranging from electricity, cooling/heating and water use. The aim of the research is to discover whether it is possible to...

Intracellular product recycling in high succinic acid producing yeast at low pH

Background: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering the cell and is again exported or even...

Effective Estimation of Dynamic Metabolic Fluxes Using 13C Labeling and Piecewise Affine Approximation: From Theory to Practical Applicability

The design of microbial production processes relies on rational choices for metabolic engineering of the production host and the process conditions. These require a systematic and quantitative understanding of cellular regulation. Therefore, a novel method for dynamic flux identification using quantitative metabolomics and 13C labeling to...

Integrated isotope-assisted metabolomics and ¹³C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger

Background: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell's metabolic regulation mechanisms. Results: In this paper, we investigate the metabolic differences and regulation mechanisms between a high glucoamylase-producing strain A. niger...

Quantitative Metabolomics and Instationary 13C-Metabolic Flux Analysis Reveals Impact of Recombinant Protein Production on Trehalose and Energy Metabolism in Pichia pastoris

Pichia pastoris has been recognized as an effective host for recombinant protein production. In this work, we combine metabolomics and instationary 13C metabolic flux analysis (INST 13C-MFA) using GC-MS and LC-MS/MS to evaluate the potential impact of the production of a Rhizopus oryzae lipase (Rol) on P. pastoris central carbon metabolism....

Glucose-methanol co-utilization in Pichia pastoris studied by metabolomics and instationary 13C flux analysis

Background Several studies have shown that the utilization of mixed carbon feeds instead of methanol as sole carbon source is beneficial for protein production with the methylotrophic yeast Pichia pastoris. In particular, growth under mixed feed conditions appears to alleviate the metabolic burden related to stress responses triggered by protein...

Quantitative analysis of relationships between fluxome and metabolome in Escherichia coli

Kinetic models, which predict the behaviour of metabolic reaction networks under different conditions, are indispensible to fully and quantitatively understand the relation between a product pathway and connected central metabolism. In this thesis the focus was to develop tools for future in vivo kinetic modeling in Escherichia coli. The...

Solvent-tolerant bioconversion: Construction and analysis of a phenol producing Pseudomonas putida S12

Organic chemicals play a fundamental role in modern civilization. Today, almost all of these chemicals are produced from oil. This leads to pollution and creates a dependency on often politically unstable oil producing countries. It is possible to make the same chemicals from sugar, using microorganisms. Sugar is produced from plants, and is...