Identification of a classical mutant in the industrial host Aspergillus niger by systems genetics: LaeA is required for citric acid production and regulates the formation of some secondary metabolites

Niu, Jing; Arentshorst, Mark; Nair, P. Deepa S.; Dai, Ziyu; Baker, Scott E.; Frisvad, Jens C.; Nielsen, Kristian F.; Punt, Peter J.; Ram, Arthur F. J.

doi:10.1534/g3.115.024067

Title: Identification of a classical mutant in the industrial host Aspergillus niger by systems genetics: LaeA is required for citric acid production and regulates the formation of some secondary metabolites

Journal Article · Fri Nov 13 00:00:00 EST 2015 · G3

DOI:https://doi.org/10.1534/g3.115.024067· OSTI ID:1249369

Niu, Jing ^[1]; Arentshorst, Mark ^[1]; Nair, P. Deepa S. ^[1]; Dai, Ziyu ^[2]; Baker, Scott E. ^[2]; Frisvad, Jens C. ^[3]; Nielsen, Kristian F. ^[3]; Punt, Peter J. ^[4]; Ram, Arthur F. J. ^[1]

Leiden Univ., Leiden (The Netherlands)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Technical Univ. of Denmark, Lyngby (Denmark)
Leiden Univ., Leiden (The Netherlands); Dutch DNA Biotech (The Netherlands)

The asexual filamentous fungus Aspergillus niger is an important industrial cell factory for citric acid production. In this study, we genetically characterized a UV-generated A. niger mutant that was originally isolated as a nonacidifying mutant, which is a desirable trait for industrial enzyme production. Physiological analysis showed that this mutant did not secrete large amounts of citric acid and oxalic acid, thus explaining the nonacidifying phenotype. As traditional complementation approaches to characterize the mutant genotype were unsuccessful, we used bulk segregant analysis in combination with high-throughput genome sequencing to identify the mutation responsible for the nonacidifying phenotype. Since A. niger has no sexual cycle, parasexual genetics was used to generate haploid segregants derived from diploids by loss of whole chromosomes. We found that the nonacidifying phenotype was caused by a point mutation in the laeA gene. LaeA encodes a putative methyltransferase-domain protein, which we show here to be required for citric acid production in an A. niger lab strain (N402) and in other citric acid production strains. The unexpected link between LaeA and citric acid production could provide new insights into the transcriptional control mechanisms related to citric acid production in A. niger. Interestingly, the secondary metabolite profile of a ΔlaeA strain differed from the wild-type strain, showing both decreased and increased metabolite levels, indicating that LaeA is also involved in regulating the production of secondary metabolites. As a result, we show that our systems genetics approach is a powerful tool to identify trait mutations.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1249369

Report Number(s):: PNNL-SA-114553

Journal Information:: G3, Vol. 6, Issue 1; ISSN 2160-1836

Publisher:: Genetics Society of AmericaCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 47 works

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Patent · Tue Mar 06 00:00:00 EST 2018 · OSTI ID:1249369

Dai, Ziyu; Baker, Scott E.

Enhanced citric acid production in aspergillus with inactivated asparagine-linked glycosylation protein 3 (ALG3), and/or increased laeA expression

Patent · Tue Dec 08 00:00:00 EST 2015 · OSTI ID:1249369

Dai, Ziyu; Baker, Scott E.

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59 BASIC BIOLOGICAL SCIENCES
organic acids
filamentous fungi
bulk segregant analysis
parasexual cycle
genome sequencing

Title: Identification of a classical mutant in the industrial host Aspergillus niger by systems genetics: LaeA is required for citric acid production and regulates the formation of some secondary metabolites

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