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Talk by Nadja A. Henke

Title: "Microbial biotechnology: from fundamental and applied microbiology to new concepts in biotechnology"
Occasion: SFB - Seminar
Start: 04.04.2024 - 16:15
Location: CellNanOs, 38/201

About the speaker:. Dr. Henke conducts research at the CZS Junior Research Group, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology, Karlsruhe.

Abstract of the talk: Carotenoids are natural pigments that accumulate in the plasma membranes of all kingdoms of life. These pigments are not only evident for photosynthesis but also possess health-related benefits making them relevant compounds for diverse industries from food and feed industries to cosmetical and health-care applications. Therefore, carotenogenesis is a widespread and interesting biosynthesis pathway to be studied both fundamentally as well as in the scope of translational research. Microbial bioprocesses are of particular interest to support the biorevolution (the economic transformation into a (circular) green economy). Corynebacterium glutamicum was discovered more than 60 years ago in Japan as a natural L-glutamate producing soil bacterium - making it one of the most powerful microorganisms in terms of industrial biotechnology (with fermentation scales of up to 200.000 L). C. glutamicum harbors the potential for carotenoid production as it accumulates the rare C50 carotenoid decaprenoxanthin in its membranes.

Fundamental investigations on carotenogenesis showed that this pathway is controlled by the transcriptional regulator CrtR that showed to be the first naturally-encoded biosensor for isoprenoid pyrophosphates1,2. Moreover, the first CRISPRi-library of C. glutamicum demonstrated to be a powerful tool to investigate impacts of gene knock-downs in a systematic manner and thus can identify bottlenecks in terms of metabolic engineering3. Based on the fundamental investigations on carotenoid biosynthesis, it could be shown that C. glutamicum is (i) a model organism to study carotenogenesis and (ii) a potent cell factory for the production of valuable carotenoids.

Metabolic engineering showed that the industrial relevant carotenoid astaxanthin could be produced in a rapid and reliable way if diverse metabolic engineering strategies are applied: (i) prevention of biosynthesis of competing pathways (ii) overexpression of genes from the precursor synthesis pathway (iii) deregulation of terminal carotenoid biosynthesis as well as (iv) construction of a membrane-fusion enzyme comprising the catalytic activities of the -carotene hydroxylase and -carotene ketolase that convert -carotene into the high-value compound astaxanthin4,5. As the heart of carotenogenesis is located at the plasma membrane, a structure-based perspective on the mechanisms of action are required in order to push metabolic engineering of this compound class to the next level. Thus further investigations have to be made in order to get a spatial-temporal resolution of the carotenoid biosynthesis at the membrane.

Bioprocess engineering tackles the transfer of overproduction strains from standard shaked cultivation systems (e.g. microtiter plates, shake flasks) to relevant stirred-tank bioreactors. Optimization of the astaxanthin production process revealed that pH is the most determining technical parameter within the process6. Based on several iterative developmental cycles a high cell density cultivation was established achieving promising titers of 180 mg/L of astaxanthin from glucose as carbon source.

Application testing of two novel astaxanthin-containing products (astaxanthin-containing biomass and astaxanthin oleoresin) demonstrates that microbial bioprocesses contribute not only to sustainable and circular economy concepts7 but also to the discovery of superior active ingredients8.