Advances in improving the biotechnological application of oleaginous fungus Mortierella alpina

Chang, Lulu; Chen, Haiqin; Tang, Xin; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.

doi:10.1007/s00253-021-11480-y

Cited by 15 publications

(11 citation statements)

References 110 publications

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“…Moreover, the expression of the gene encoding the phosphoenolpyruvate kinase (EC: 4.1.1.49; FPKM value decreased from 169.83 in the TA group to 126.17 in the TB group), which catalyzes the conversion of oxaloacetate to phosphoenolpyruvate, was decreased, ultimately decreasing the consumption of pyruvate and increasing the production of acetyl-CoA, catalyzed by pyruvate dehydrogenase (EC: 2.3.1.12). Second, acetyl-CoA is generated by the oxidation of both fatty acids and amino acids in the mitochondria [39]. Our enrichment analysis results based on the KEGG database showed that, under cold stress, the DEGs in M. alpina were significantly enriched in the pathway of fatty acid degradation.…”

Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 73%

“…As one of the important types of starting materials for fatty acid synthesis [38], acetyl-CoA is generally produced in one of two ways in M. alpina. First, the pyruvate is catalyzed by both the mitochondrial pyruvate dehydrogenase complex and the citrate synthase to produce citrate, which is cleaved by ATP:citrate lyase to generate acetyl-CoA [39]. Our results showed that the genes encoding hexokinase (EC: 2.…”

Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 83%

“…Agricultural microorganisms have been used widely to produce microbial food, with the synthesis and metabolism of fatty acids extensively investigated. In particular, the metabolic pathway of fatty acid metabolism in M. alpina is well explored and unsaturated As the key reducing agent in many metabolic pathways, NADPH is also a key cofactor for fatty acid synthesis and desaturation [39]. However, it is not clear how NADPH is mainly generated in M. alpina.…”

Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 99%

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Transcriptomic Characterizations of the Molecular Mechanisms Regulating Lipid Production and Composition in Mortierella alpina in Response to Cold Stress

et al. 2022

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Cold stress causes changes in the lipid composition of Mortierella alpina. In order to investigate the molecular mechanisms of M. alpina in response to cold stress, transcriptome analyses were performed on three groups of M. alpina cultured at (1) 25 °C, (2) 15 °C, and (3) first at 25 °C for 2 days and then 15 °C for 7 days, respectively. The results of a gas chromatography–mass spectrometry (GC–MS) analysis suggested that, compared with 25 °C conditions, dry weight and lipid production were significantly decreased in M. alpina grown at 15 °C, with a total of 1552 differentially expressed genes (DEGs) identified in response to cold stress. The quantitative real-time PCR (qRT-PCR) analysis was conducted to verify the expression patterns of six DEGs involved in lipid metabolism. Results of the enrichment analyses of the DEGs based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases showed that fatty acid compositions were regulated by genes involved in the glycolysis pathway, fatty acid synthesis, the pentose phosphate pathway, the glycerolipid pathway, the tricarboxylic acid (TCA) cycle, and the glycerophospholipid pathway. Our study provided solid experimental evidence and novel insights into the metabolic engineering and the molecular mechanisms regulating the response to cold stress in M. alpina.

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Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 73%

Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 83%

Section: Acetyl-coa and Nadph Metabolismmentioning

confidence: 99%

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Transcriptomic Characterizations of the Molecular Mechanisms Regulating Lipid Production and Composition in Mortierella alpina in Response to Cold Stress

et al. 2022

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“…Nitrogen deprivation can increase the generation of PUFAs by rerouting the glycolytic flow of carbon backbones into fatty acid biosynthesis because certain amino acids, such as BCAAs, when broken down, release acetyl-CoA ( Chang et al, 2021 ). The transcriptome data in this study showed that the pathways for Val-Leu-Ile metabolism were upregulated when malate was added, which is another pathway for acetyl-CoA generation.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of malate-induced Schizochytrium sp. FJU-512 reveals a novel pathway for biosynthesis of docosahexaenoic acid with enhanced expression of genes responsible for acetyl-CoA and NADPH accumulation

Zhang

Gao

et al. 2022

Front. Microbiol.

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Schizochytrium is one of the few oleaginous microalgae that produce docosahexaenoic acid (DHA)-rich lipids. In this study, global changes in gene expression levels of Schizochytrium sp. FJU-512 cultured with malate in a 15 l-bioreactor was analyzed using comparative transcriptomics. The changes were found mainly in the genes involved in oxidative phosphorylation, β-oxidation, and pentose phosphate pathways. Consequently, the global changes in genes associated with the pathways could lead to an increase in the influx throughputs of pyruvate, branched-chain amino acids, fatty acids, and vitamin B6. Our transcriptome analysis indicated pyruvate dehydrogenase E2 component and acetolactate synthase I/II/III large subunit as major contributors to acetyl-CoA biosynthesis, whereas glucose-6-phosphate dehydrogenase was indicated as the major contributor to the biosynthesis of NADPH. An increase in DHA titer of up to 22% was achieved with the addition of malate to the fed-batch culture of Schizochytrium sp. FJU-512. This study provides an alternate method to enhance DHA production in Schizochytrium sp. FJU-512 through malate induced upregulation of genes responsible for acetyl-CoA and NADPH biosynthesis.

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“…The PUFA production can be boosted by supplementation with animal fat by-products [12] or odd-chain alkanes that increase the yield of C15, C17, and C19 odd-chain fatty acids [13]. Moreover, nitrogen deprivation can drive PUFA production by redirection of the glycolytic flux of carbon backbones into fatty acid biosynthesis because decomposition of some amino acids, including BCAAs, is accompanied with the release of acetyl-CoA, the building block for fatty acids [14]. Indeed, the BCAA pathway enzymes are coregulated with the lipid metabolism in oleaginous fungi [5].…”

Section: Introductionmentioning

confidence: 99%

Regulation of the Leucine Metabolism in Mortierella alpina

Sonnabend

Seiler

Gressler

2022

JoF

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The oleaginous fungus Mortierella alpina is a safe source of polyunsaturated fatty acids (PUFA) in industrial food and feed production. Besides PUFA production, pharmaceutically relevant surface-active and antimicrobial oligopeptides were isolated from this basal fungus. Both production of fatty acids and oligopeptides rely on the biosynthesis and high turnover of branched-chain-amino acids (BCAA), especially l-leucine. However, the regulation of BCAA biosynthesis in basal fungi is largely unknown. Here, we report on the regulation of the leucine, isoleucine, and valine metabolism in M. alpina. In contrast to higher fungi, the biosynthetic genes for BCAA are hardly transcriptionally regulated, as shown by qRT-PCR analysis, which suggests a constant production of BCAAs. However, the enzymes of the leucine metabolism are tightly metabolically regulated. Three enzymes of the leucine metabolism were heterologously produced in Escherichia coli, one of which is inhibited by allosteric feedback loops: The key regulator is the α-isopropylmalate synthase LeuA1, which is strongly disabled by l-leucine, α-ketoisocaproate, and propionyl-CoA, the precursor of the odd-chain fatty acid catabolism. Its gene is not related to homologs from higher fungi, but it has been inherited from a phototrophic ancestor by horizontal gene transfer.

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Advances in improving the biotechnological application of oleaginous fungus Mortierella alpina

Cited by 15 publications

References 110 publications

Transcriptomic Characterizations of the Molecular Mechanisms Regulating Lipid Production and Composition in Mortierella alpina in Response to Cold Stress

Transcriptomic Characterizations of the Molecular Mechanisms Regulating Lipid Production and Composition in Mortierella alpina in Response to Cold Stress

Transcriptome analysis of malate-induced Schizochytrium sp. FJU-512 reveals a novel pathway for biosynthesis of docosahexaenoic acid with enhanced expression of genes responsible for acetyl-CoA and NADPH accumulation

Regulation of the Leucine Metabolism in Mortierella alpina

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