Genetic engineering of the red yeast Xanthophyllomyces dendrorhous for high-yield synthesis of carotenoids such as astaxanthin, zeaxanthin and phytoene

Economic chemical synthesis of carotenoid as colorants, food and feed additives is restricted to a few compounds, whereas exploitation of natural sources may be restricted by low concentrations. To increase carotenoid production in fungi, genetic pathway engineering is a method of choice. Additionally, pathways can be extended to novel carotenoid products.

The red basidiomycetous yeast Xanthophyllomyces dendrorhous (with Phaffia rhodozyma as its anamorphic state) was successfully developed as a carotenoid production system. Plasmids for gene integration into the genome have been developed. Knock-out of genes and knock-in was successful. The genetic modification strategies involved generation and selection of suitable mutants, pathway enhancement and pathway extension. This combinatorial approaches led to high-yield prototypes for astaxanthin (1), zeaxanthin (2) and phytoene (3). Furthermore, novel carotenoids such as multi-hydroxy β-carotene derivatives could be generated in X. dendrorhous (4).

Acknowledgements: This work was supported as the ERA-IB project PROCAR through the German Federal Ministry of Education and Research (BMBF) (FKZ 031A569).

1. S. Gassel, J. Breitenbach, G. Sandmann (2014) Genetic engineering of the complete carotenoid pathway towards enhanced astaxanthin formation in Xanthophyllomyces dendrorhous starting from a high-yield mutant. Appl. Microbiol. Biotechnol. 98, 345-350.
2. H. Pollmann, J. Breitenbach, G. Sandmann (2017) Engineering of the carotenoid pathway in Xanthophyllomyces dendrorhous leading to the synthesis of zeaxanthin. Appl. Microbiol. Biotechnol. 101:103–111.
3. H. Pollmann, J. Breitenbach, G. Sandmann (2017) Development of Xanthophyllomyces dendrorhous as a production system for the colorless carotene phytoene. J. Biotechnol. 247, 34–41.
4. H. Pollmann, J. Breitenbach, H. Wolff, H. B. Bode, G. Sandmann (2017) Combinatorial biosynthesis of novel multi-hydroxy carotenoids in the red yeast Xanthophyllomyces dendrorhous. J. Fungi 3, 9.