Rewiring metabolic flux to simultaneously improve malate production and eliminate by-product succinate accumulation by Myceliophthora thermophila.

ABSTRACT: Although a high titre of malic acid is achieved by filamentous fungi, by-product succinic acid accumulation leads to a low yield of malic acid and is unfavourable for downstream processing. Herein, we conducted a series of metabolic rewiring strategies in a previously constructed Myceliophthora thermophila to successfully improve malate production and abolish succinic acid accumulation. First, a pyruvate carboxylase CgPYC variant with increased activity was obtained using a high-throughput system and introduced to improve malic acid synthesis. Subsequently, shifting metabolic flux to malate synthesis from mitochondrial metabolism by deleing mitochondrial carriers of pyruvate and malate, led to a 53.7% reduction in succinic acid accumulation. The acceleration of importing cytosolic succinic

SUBMITTER: Gu S 

PROVIDER: S-EPMC10884987 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature