Comparative genomics analysis of a series of Yarrowia lipolytica WSH-Z06 mutants with varied capacity for α-ketoglutarate production

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.