Identification of a specific exporter that enables high production of aconitic acid in Aspergillus pseudoterreus

Deng, Shuang; Kim, Joonhoon; Pomraning, Kyle R.; Gao, Yuqian; Evans, James E.; Hofstad, Beth A.; Dai, Ziyu; Webb-Robertson, Bobbie-Jo M.; Powell, Samantha M.; Novikova, Irina V.; Munoz, Nathalie; Kim, Young-Mo; Swita, Marie S.; Robles, Ana L.; Lemmon, Teresa L.; Duong, Rylan D.; Nicora, Carrie D.; Burnum-Johnson, Kristin E.; Magnuson, Jon K.

doi:10.1016/j.ymben.2023.09.011

Identification of a specific exporter that enables high production of aconitic acid in Aspergillus pseudoterreus

Journal Article · Fri Sep 29 00:00:00 EDT 2023 · Metabolic Engineering

DOI:https://doi.org/10.1016/j.ymben.2023.09.011· OSTI ID:2305375

^[1]; ^[1]; ^[1]; Gao, Yuqian ^[1]; Evans, James E. ^[2]; Hofstad, Beth A. ^[1]; Dai, Ziyu ^[1]; Webb-Robertson, Bobbie-Jo M. ^[2]; ^[2]; Novikova, Irina V. ^[2]; Munoz, Nathalie ^[1]; ^[1]; Swita, Marie S. ^[2]; Robles, Ana L. ^[1]; Lemmon, Teresa L. ^[2]; Duong, Rylan D. ^[2]; ^[2]; ^[1]; ^[1]

USDOE Agile BioFoundry, Emeryville, CA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Aconitic acid is an unsaturated tricarboxylic acid that is attractive for its potential use in the manufacture of biodegradable and biocompatible polymers, plasticizers, and surfactants. Previously Aspergillus pseudoterreus was engineered as a platform to produce aconitic acid by deleting the cadA (cis-aconitic acid decarboxylase) gene in the itaconic acid biosynthetic pathway. In this study aconitic acid transporter gene (aexA) was identified using comparative global discovery proteomics analysis between the wild-type and cadA deletion strains. Deletion of aexA almost eliminated aconitic acid secretion, while its overexpression led to a significant increase in aconitic acid production. Transportation of aconitic acid across the plasma membrane is a key limiting step. In vitro proteoliposome transport assay further validated AexA’s function and its substrate specificity. This research provides new approaches to efficiently pinpoint and characterize exporters of fungal organic acids and accelerate the metabolic engineering to improve secretion capability and lower cost for bioproduction.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation. Bioenergy Technologies Office (BETO); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2305375

Report Number(s):: PNNL-SA--181297

Journal Information:: Metabolic Engineering, Journal Name: Metabolic Engineering Vol. 80; ISSN 1096-7176

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Aconitic acid (AA)
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Identification of a specific exporter that enables high production of aconitic acid in Aspergillus pseudoterreus

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