Timo Hardiman

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Sustained progress in metabolic engineering methodologies has stimulated new efforts toward optimizing fungal production strains such as through metabolite analysis of Penicillium chrysogenum industrial-scale processes. Accurate intracellular metabolite quantification requires sampling procedures that rapidly stop metabolism (quenching) and avoid metabolite(More)
One fundamental shortcoming of biotechnological processes operating under carbon-limiting conditions is the high-energy demand (maintenance) of the cells. Although the function of the central carbon metabolism in supplying precursors and energy for biosynthesis has been thoroughly characterized, its regulation and dynamic behaviour during carbon-limited(More)
The majority of dynamic gene regulatory network (GRN) models are comprised of only a few genes and do not take multiple transcription regulation into account. The models are conceived in this way in order to minimize the number of kinetic parameters. In this paper, we propose a new approach for predicting kinetic parameters from DNA-binding site sequences(More)
Current messenger RNA (mRNA) quantification methods are sophisticated tools for the analysis of gene regulation. However, these methods are not suitable for more complex quantitative approaches such as the mathematical modeling of the in vivo regulation of transcription where dynamic cytosolic mRNA concentrations need to be taken into consideration. In the(More)
The intracellular alarmone guanosine 3',5'-bis(diphosphate) (ppGpp) has been thoroughly investigated over the past 40 years and has become one of the best-known effectors in bacterial physiology. ppGpp is also of great importance for biotechnological applications. Systems biology research, involving experimental and mathematical approaches, has contributed(More)
The MEtabolic MOdel research and development System (MEMOSys) is a versatile database for the management, storage and development of genome-scale models (GEMs). Since its initial release, the database has undergone major improvements, and the new version introduces several new features. First, the novel concept of derived models allows users to create model(More)
Over the past 10 years, sophisticated powerful techniques have been developed for the quantification of messenger RNA (mRNA) and ribosomal RNA (rRNA), enabling researchers in science, industry, and molecular medicine to explore gene expression. These techniques require the (reverse) transcription of analyte RNA, hybridization with synthetic(More)
The filamentous fungus Penicillium chrysogenum is one of the most important production organism for β-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase(More)
et al. MEMOSys 2.0: an update of the bioinformatics database for genome-scale models and genomic data. The MEtabolic MOdel research and development System (MEMOSys) is a versatile database for the management, storage and development of genome-scale models (GEMs). Since its initial release, the database has undergone major improvements , and the new version(More)
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