Highly efficient neutralizer-free L-malic acid production using engineered Saccharomyces cerevisiae
Author(s)
Type
Journal Article
Abstract
In industrial bioproduction of organic acids, numerous neutralizers are required which substantially increases production costs and burdens the environment. To address this challenge, a Saccharomyces cerevisiae mutant (named TAMC) with a low pH tolerance (pH 2.3) was isolated by adaptive laboratory evolution. Taking the synthesis of l-malic acid as an example, the malate dehydrogenase 3 without signal peptide (MDHΔSKL) and pyruvate carboxylase 2 (PYC2) were overexpressed in cytoplasmic synthesis pathway, and the l-malic acid titer increased 5.6-fold. Subsequently, the malic acid transporter SpMae1 was designed, and the extracellular l-malic acid titer was increased from 7.3 to 73.6 g/L. Furthermore, by optimizing the synthesis of the precursor pyruvate, the titer reached 81.8 g/L. Finally, without any neutralizer, the titer in the 3-L bioreactor reached 232.9 g/L, the highest l-malic acid titer reported to date. Herein, the engineered l-malic acid overproducer paves the way for the large-scale green production of l-malic acid.
Date Issued
2023-02-01
Date Acceptance
2023-01-03
Citation
Bioresource Technology, 2023, 370
ISSN
0960-8524
Publisher
Elsevier
Journal / Book Title
Bioresource Technology
Volume
370
Copyright Statement
Copyright © Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36608859
PII: S0960-8524(23)00006-8
Subjects
Acid tolerance
Agricultural Engineering
Agriculture
Biotechnology & Applied Microbiology
DEHALOGENASE
Energy & Fuels
EVOLUTION
FERMENTATION
Life Sciences & Biomedicine
L-malic acid
LOW PH
MALATE
MECHANISMS
Neutralizer-free bioproduction
ORGANIC-ACIDS
OVEREXPRESSION
Saccharomyces cerevisiae
Science & Technology
SUCCINIC ACID
Technology
TOLERANCE
Transporter engineering
Publication Status
Published
Coverage Spatial
England
Article Number
128580
Date Publish Online
2023-01-03