Scaling-down biopharmaceutical production processes via a single multi-compartment bioreactor (SMCB).

Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale-down reactors. However, commonly applied multi-compartment approaches comprising multiple reactors impose a biasing shear stress caused by pumping.

FAIR research data management as community approach in bioengineering.

Research data management (RDM) requires standards, policies, and guidelines. Findable, accessible, interoperable, and reusable (FAIR) data management is critical for sustainable research. Therefore, collaborative approaches for managing FAIR-structured data are becoming increasingly important for long-term, sustainable RDM.

Synthetic mutualism in engineered mutant strains as functional basis for microbial production consortia.

In nature, microorganisms often reside in symbiotic co-existence providing nutrition, stability, and protection for each partner by applying "division of labor." This principle may also be used for the overproduction of targeted compounds in bioprocesses. It requires the engineering of a synthetic co-culture with distributed tasks for each partner.

CRISPRi enables fast growth followed by stable aerobic pyruvate formation in without auxotrophy.

CRISPR interference (CRISPRi) was applied to enable the aerobic production of pyruvate in MG1655 under glucose excess conditions by targeting the promoter regions of or . Knockdown strains were cultivated in aerobic shaking flasks and the influence of inducer concentration and different sgRNA binding sites on the production of pyruvate was measured. Targeting the promoter regions of or triggered pyruvate production during the exponential phase and reduced expression of .

Compartment-specific C metabolic flux analysis reveals boosted NADPH availability coinciding with increased cell-specific productivity for IgG1 producing CHO cells after MTA treatment.

Increasing cell-specific productivities (CSPs) for the production of heterologous proteins in Chinese hamster ovary (CHO) cells is an omnipresent need in the biopharmaceutical industry. The novel additive 5'-deoxy-5'-(methylthio)adenosine (MTA), a chemical degradation product of S-(5'-adenosyl)-ʟ-methionine (SAM) and intermediate of polyamine biosynthesis, boosts the CSP of IgG1-producing CHO cells by 50%. Compartment-specific C flux analysis revealed a fundamental reprogramming of the central metabolism after MTA addition accompanied by cell-cycle arrest and increased cell volumes.

Micro-aerobic production of isobutanol with engineered .

KT2440 is emerging as a promising microbial host for biotechnological industry due to its broad range of substrate affinity and resilience to physicochemical stresses. Its natural tolerance towards aromatics and solvents qualifies this versatile microbe as promising candidate to produce next generation biofuels such as isobutanol. In this study, we scaled-up the production of isobutanol with from shake flask to fed-batch cultivation in a 30 L bioreactor.

A novel LysR-type regulator negatively affects biosynthesis of the immunosuppressant brasilicardin.

Brasilicardin A (BraA) is a promising immunosuppressive compound produced naturally by the pathogenic bacterium IFM 0406. Heterologous host expression of brasilicardin gene cluster showed to be efficient to bypass the safety issues, low production levels and lack of genetic tools related with the use of native producer. Further improvement of production yields requires better understanding of gene expression regulation within the BraA biosynthetic gene cluster (Bra-BGC); however, the only so far known regulator of this gene cluster is Bra12.

Comparison of l-tyrosine containing dipeptides reveals maximum ATP availability for l-prolyl-l-tyrosine in CHO cells.

Increasing markets for biopharmaceuticals, including monoclonal antibodies, have triggered a permanent need for bioprocess optimization. Biochemical engineering approaches often include the optimization of basal and feed media to improve productivities of Chinese hamster ovary (CHO) cell cultures. Often, l-tyrosine is added as dipeptide to deal with its poor solubility at neutral pH.

Engineering KT2440 for the production of isobutanol.

We engineered for the production of isobutanol from glucose by preventing product and precursor degradation, inactivation of the soluble transhydrogenase SthA, overexpression of the native and genes, and implementation of the feedback-resistant acetolactate synthase AlsS from , ketoacid decarboxylase KivD from , and aldehyde dehydrogenase YqhD from . The resulting strain Iso2 produced isobutanol with a substrate specific product yield ( ) of 22 ± 2 mg per gram of glucose under aerobic conditions. Furthermore, we identified the ketoacid decarboxylase from to be a suitable alternative for isobutanol production, since replacement of from in Iso2 by the variant from yielded an identical Y.

Synergistically applying 1-D modeling and CFD for designing industrial scale bubble column syngas bioreactors.

The reduction of greenhouse gas emissions and future perspectives of circular economy ask for new solutions to produce commodities and fine chemicals. Large-scale bubble columns operated by gaseous substrates such as CO, CO, and H to feed acetogens for product formations could be promising approaches. Valid in silico predictions of large-scale performance are needed to dimension bioreactors properly taking into account biological constraints, too.

Zero-growth bioprocesses: A challenge for microbial production strains and bioprocess engineering.

Microbial fermentation of renewable feedstocks is an established technology in industrial biotechnology. Besides strict aerobic or anaerobic modes of operation, novel innovative and industrially applicable fermentation processes were developed connecting the advantages of aerobic and anaerobic conditions in a combined production approach. As a consequence, rapid aerobic biomass formation to high cell densities and subsequent anaerobic high-yield and zero-growth production is realized.