bZIP transcription factor FabR: Redox-dependent mechanism controlling docosahexaenoic acid biosynthesis and H2O2 stress response in Schizochytrium sp.

Liu, Yana; Han, Xiao; Dai, Yujie; Chen, Zhi

doi:10.1016/j.freeradbiomed.2023.11.027

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…In our previous studies, we have identified zinc finger protein LipR and bZIP transcription factor FabR which both simultaneously represses the transcription of fatty acids synthase and PUFA synthase genes in Schizochytrium sp. [ 27 , 28 ]. Therefore, systematical screening and validation of the regulators involved in lipid accumulation will help to elucidate the molecular mechanisms regulating lipid saturation and the complex regulatory networks of DHA synthesis in thraustochytrids.…”

Section: Discussionmentioning

confidence: 99%

Selectively superior production of docosahexaenoic acid in Schizochytrium sp. through engineering the fatty acid biosynthetic pathways

Liu,

Han,

Chen

et al. 2024

Biotechnol Biofuels

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Background Schizochytrium sp. is commercially used for production of docosahexaenoic acid (DHA). Schizochytrium sp. utilizes the polyketide synthase complex (PKS) and a single type I fatty acid synthase (FAS) to synthesize polyunsaturated fatty acids and saturated fatty acids, respectively. The acyl carrier protein (ACP) domains of FAS or PKS are used to load acyl groups during fatty acids biosynthesis. Phosphopantetheinyl transferase (PPTase) transfers the pantetheine moiety from Coenzyme A to the conserved serine residue of an inactive ACP domain to produce its active form. Results In this study, in order to improve production and content of DHA, we decreased the expression of fas, strengthened the expression of the PKS pathway, and enhanced the supply of active ACP in Schizochytrium sp. ATCC20888. Weakening the expression of fas or disruption of orfA both led to growth defect and reduction of lipid yields in the resulting strains WFAS and DPKSA, indicating that both FAS and PKS were indispensable for growth and lipid accumulation. Although WFAS had a higher DHA content in total fatty acids than the wild-type strain (WT), its growth defect and low DHA yield hinders its use for DHA production. Overexpression of the orfAB, orfC, orfC-DH (truncated orfC), or ppt promoted DHA and lipid production, respectively. The yields and contents of DHA were further increased by combined overexpression of these genes. Highest values of DHA yield (7.2 g/L) and DHA content (40.6%) were achieved in a recombinant OPKSABC-PPT, ⁓56.5% and 15.3% higher than the WT values, respectively. Conclusions This study demonstrates that genetic engineering of the fatty acid biosynthetic pathways provides a new strategy to enhance DHA production in Schizochytrium.

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Section: Discussionmentioning

confidence: 99%

Selectively superior production of docosahexaenoic acid in Schizochytrium sp. through engineering the fatty acid biosynthetic pathways

Liu,

Han,

Chen

et al. 2024

Biotechnol Biofuels

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“…The production of total lipids and docosahexaenoic acid in fungus was enhanced by 30.1% and 46.5%, respectively, upon deletion of the fabR gene (bZIP-type TF) in Schizochytrium sp. ( 40 ). Four fatty acid concentration in B. bassiana was significantly reduced as a result of ablation of BbHapX (bZIP-type TF) ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

The basic leucine zipper domain (bZIP) transcription factor BbYap1 promotes evasion of host humoral immunity and regulates lipid homeostasis contributing to fungal virulence in Beauveria bassiana

Wang,

Chen,

Zhang

et al. 2024

mSphere

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Basic leucine zipper domain transcription factors (TFs), of which yeast activator protein (Yap) is a significant class, are crucial for the development of sclerotia, the stress response, vegetative growth, and spore adhesion. Nevertheless, nothing is known about how Yap TFs contribute to the pathogenicity of entomopathogenic fungus. In this work, Beauveria bassiana was used to identify and knock out the yeast gene BbYap1 , which is similar to Yap. The BbYap1 gene deletion has an impact on lipid homeostasis of B. bassiana ; oleic acid, for example, dropped by 95.69%. The BbYap1 mutant exhibited much less virulence and vegetative development in comparison to the wild strain, while demonstrating a greater sensitivity to chemical stress. It is noteworthy that the physiological abnormalities brought on by BbYap1 deletion were largely repaired by the addition of exogenous oleic acid, as seen by the notable increase in insect survival in the blood cavity injection group. Following infection with the BbYap1 mutant, the host exhibits a considerable down-regulation of the expression of β-1,3-glucan recognition protein, gallerimycin, gloverin, and moricin-like protein genes. Likewise, the introduction of exogenous oleic acid markedly increased the host’s expression of the aforementioned genes. In summary, BbYap1 regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development. IMPORTANCE Entomopathogenic fungi (EPF) offer an effective and eco-friendly alternative to curb insect populations in biocontrol strategy. When EPF enter the hemolymph of their host, they encounter a variety of stress reactions, such as immunological and oxidative stress. Basic leucine zipper domain transcription factors, of which yeast activator protein (Yap) is a significant class, have diverse biological functions related to metabolism, development, reproduction, conidiation, stress responses, and pathogenicity. This study demonstrates that BbYap1 of Beauveria bassiana regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development. These findings offer fresh perspectives for comprehending molecular roles of YAP in EPF.

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“…Furthermore, FabR was found to be involved in the H 2 O 2 stress response in Schizochytrium. The deletion of fabR led to enhanced growth rate, elevated DHA and lipid production (an increase of 30.1% and 46.5%, respectively), and improved antioxidant capacity compared to WT [79]. A RING finger domain-containing protein was identified in Schizochytrium, and it significantly increased fatty acid and β-carotene content, especially C14:0 [80].…”

Section: Schizochytriummentioning

confidence: 98%

“…The transcription regulation network related to fatty acids has been elucidated in recent years. The zinc finger protein LipR and the bZIP-type transcription factor FabR were both identified as negative regulators of lipid biosynthesis in Schizochytrium, exerting direct control over the transcription of genes encoding PKS synthase and FAS synthase [78,79]. The deletion of the lipR gene resulted in a significant increase of 33% in total lipids and 48% in DHA production [78].…”

Section: Schizochytriummentioning

confidence: 99%

Engineering Fatty Acid Biosynthesis in Microalgae: Recent Progress and Perspectives

Song,

Wang,

Chen

et al. 2024

Marine Drugs

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Microalgal lipids hold significant potential for the production of biodiesel and dietary supplements. To enhance their cost-effectiveness and commercial competitiveness, it is imperative to improve microalgal lipid productivity. Metabolic engineering that targets the key enzymes of the fatty acid synthesis pathway, along with transcription factor engineering, are effective strategies for improving lipid productivity in microalgae. This review provides a summary of the advancements made in the past 5 years in engineering the fatty acid biosynthetic pathway in eukaryotic microalgae. Furthermore, this review offers insights into transcriptional regulatory mechanisms and transcription factor engineering aimed at enhancing lipid production in eukaryotic microalgae. Finally, the review discusses the challenges and future perspectives associated with utilizing microalgae for the efficient production of lipids.

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bZIP transcription factor FabR: Redox-dependent mechanism controlling docosahexaenoic acid biosynthesis and H2O2 stress response in Schizochytrium sp.

Cited by 4 publications

References 42 publications

Selectively superior production of docosahexaenoic acid in Schizochytrium sp. through engineering the fatty acid biosynthetic pathways

Selectively superior production of docosahexaenoic acid in Schizochytrium sp. through engineering the fatty acid biosynthetic pathways

The basic leucine zipper domain (bZIP) transcription factor BbYap1 promotes evasion of host humoral immunity and regulates lipid homeostasis contributing to fungal virulence in Beauveria bassiana

Engineering Fatty Acid Biosynthesis in Microalgae: Recent Progress and Perspectives

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