Journal
JOURNAL OF BIOTECHNOLOGY
Volume 239, Issue -, Pages 76-82Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jbiotec.2016.10.008
Keywords
Yarrowia lipolytica; alpha-Ketoglutarate; High-throughput screening; Carboxylic acid; Keto acid; Genomics sequencing
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Funding
- National High Technology Research and Development Program of China (863 Program) [2015AA021003, 2015AA021005]
- National Natural Science Foundation of China [31130043, 21276109]
- Author of National Excellent Doctoral Dissertation of PR China (FANEDD) [201256]
- Program for New Century Excellent Talents in University [NCET-12-0876]
- 111 Project [111-2-06]
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Yarrowia lipolytica is one of the most intensively investigated alpha-ketoglutaric acid (alpha-KG) producers, and metabolic engineering has proven effective for enhancing production. However, regulation of alpha-KG metabolism remains poorly understood. Genetic engineering of new strains is accompanied by potential safety concerns in some countries and regions. A series of mutants with varied capacity for alpha-KG production were obtained using random mutagenesis of Y. lipolytica WSH-206. Comparative genomics analysis was implemented to identify genes candidates associated with alpha-KG production. Manipulation of genes regulating mitochondrial biogenesis and energy metabolism could improve alpha-KG production, while genes involved in regulating transformation between keto acids and amino acids may decrease production. One gene associated with cell cycle control well represented in all mutants, whereas this gene involved in cell concentration do not appear to influence alpha-KG production. The results shed light on alpha-KG production in eukaryotic cells, and pave the way for a high-throughput screening and random mutagenesis method for enhancing alpha-KG production. (C) 2016 Elsevier B.V. All rights reserved.
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