A new version of this entry is available:

Loading...
Thumbnail Image
Article
2021

Orotic acid production by Yarrowia lipolytica under conditions of limited pyrimidine

Abstract (English)

Orotic acid (OA) is an intermediate of the pyrimidine biosynthesis with high industrial relevance due to its use as precursor for production of biochemical pyrimidines or its use as carrier molecule in drug formulations. It can be produced by fermentation of microorganisms with engineered pyrimidine metabolism. In this study, we surprisingly discovered the yeast Yarrowia lipolytica as a powerful producer of OA. The overproduction of OA in the Y. lipolytica strain PO1f was found to be caused by the deletion of the URA3 gene which prevents the irreversible decarboxylation of OA to uridine monophosphate. It was shown that the lack of orotidine‐5′‐phosphate decarboxylase was the reason for the accumulation of OA inside the cell since a rescue mutant of the URA3 deletion in Y. lipolytica PO1f completely prevented the OA secretion into the medium. In addition, pyrimidine limitation in the cell massively enhanced the OA accumulation followed by secretion due to intense overflow metabolism during bioreactor cultivations. Accordingly, supplementation of the medium with 200 mg/L uracil drastically decreased the OA overproduction by 91%. OA productivity was further enhanced in fed‐batch cultivation with glucose and ammonium sulfate feed to a maximal yield of 9.62 ± 0.21 g/L. Y. lipolytica is one of three OA overproducing yeasts described in the literature so far, and in this study, the highest productivity was shown. This work demonstrates the potential of Y. lipolytica as a possible production organism for OA and provides a basis for further metabolic pathway engineering to optimize OA productivity.

File is subject to an embargo until

This is a correction to:

A correction to this entry is available:

This is a new version of:

Notes

Publication license

Publication series

Published in

Yeast, 39 (2021), 3, 230-240. https://doi.org/10.1002/yea.3673. ISSN: 1097-0061
Faculty
Institute

Examination date

Supervisor

Edition / version

Citation

DOI

ISSN

ISBN

Language
English

Publisher

Publisher place

Classification (DDC)
660 Chemical engineerin

Original object

Standardized keywords (GND)

BibTeX

@article{Swietalski2021, url = {https://hohpublica.uni-hohenheim.de/handle/123456789/16776}, doi = {10.1002/yea.3673}, author = {Swietalski, Paul and Hetzel, Frank and Klaiber, Iris et al.}, title = {Orotic acid production by Yarrowia lipolytica under conditions of limited pyrimidine}, journal = {Yeast}, year = {2021}, volume = {39}, number = {3}, }