Design of Superior Cell Factories Based on Systems Wide Omics Analysis

Abstract Background: Propionic acid (PA), a potential building block for C3-based bulk chemicals, is used as a food preservative and antifungal agent because of the antimicrobial properties of its calcium-, potassium-, and sodium salts, as well as in the manufacture of pharmaceuticals, perfumes, pesticides and fungicides. However, industrial development of PA is seriously inhibited by oxygen stress, acid stress and glucose-induced osmotic stress concentration on account of the characteristic of Propionibacterium acidipropionici. To alleviate inhibition and increase PA production, enhancement P. acidipropionici tolerance to cross stress may be an effective strategy. Results: In this study, we first performed a combination of metabolic engineering (deletion of ldh and poxB and overexpression of mmc) with evolutionary engineering (selection under oxygen stress, acid stress and osmotic stress) in P. acidipropionici. The results indicated the mutants received superior physiological activity, especially the mutant III exhibited steady 1.5-3.5 folds higher growth property and further 37.1% PA titer and 37.8% PA productivity increase than the wildtype. Moreover, omics analysis revealed the determinants such as Dps , GroES , dnaK , ADI and GAD referred to the acid adaptation of microbes were positively mobilized. ABC-type glycine betaine referred to the adaptability to osmotic stress was detected to be 2-4 folds up-regulated. More than 2-fold down-regulation of NADH oxidase and almost 3-fold up-regulation of SOD and POD were observed in three mutants. Moreover, an approximately 2.5-fold upregulation of mmc was also found.Conclusion: The multi-omics analysis revealed the multidirectional variation tendency of P. acidipropionici under cross stress and provided in-depth insights into the mechanism of tolerance and high production of PA, which layed the foundation for construction of microbial cell factories.

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Multi-Omics Analysis of Respiratory Specimen Characterizes Baseline Molecular Determinants Associated with COVID-19 Diagnosis and Outcome

SSRN Electronic Journal ◽

10.2139/ssrn.3681981 ◽

2020 ◽

Author(s):

Jaswinder Singh Maras ◽

Shvetank Sharma ◽

Adil Bhat ◽

sheetalnath Rooge ◽

Reshu Agarwal ◽

...

Keyword(s):

Respiratory Specimen ◽

Omics Analysis ◽

Molecular Determinants

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Heterologous Synthesis and Recovery of Advanced Biofuels from Bacterial Cell Factories

Protein and Peptide Letters ◽

10.2174/0929866525666180122125237 ◽

2018 ◽

Vol 25 (2) ◽

pp. 120-128 ◽

Cited By ~ 2

Author(s):

Sana Malik ◽

Ifrah Afzal ◽

Muhammad Aamer Mehmood ◽

Huda Al Doghaither ◽

Sawsan Abdulaziz Rahimuddin ◽

...

Keyword(s):

Bacterial Cell ◽

Advanced Biofuels ◽

Cell Factories

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Multi-Omics Analysis of Anti-Inflammatory Action of Alkaline Extract of the Leaves of Sasa sp.

Journal of Clinical Medicine ◽

10.3390/jcm10102100 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2100

Author(s):

Hiroshi Sakagami ◽

Sachie Nakatani ◽

Ayame Enomoto ◽

Sana Ota ◽

Miku Kaneko ◽

...

Keyword(s):

Culture Medium ◽

Growth Stimulation ◽

Pge2 Production ◽

Oral Diseases ◽

Total Glutathione ◽

Simultaneous Treatment ◽

Alkaline Extract ◽

Omics Analysis ◽

Anti Inflammatory ◽

Inflammatory Action

Efficient utilization of alkaline extracts of several plants for the treatment of oral diseases has been reported. To investigate the mechanism of anti-inflammatory activity of alkaline extract of the leaves of Sasa sp. (SE), multi-omics analysis using metabolomics and DNA array was performed. Human gingival fibroblasts (HGFs) were treated for IL-1β to induce inflammation (detected by PGE2 production in culture medium) in the presence or absence of SE. Both IL-1β and SE showed slight hormetic growth stimulation against HGF. SE inhibited PGE2 production dose- and time-dependently. Its inhibitory action was more pronounced by first treating the cells with SE, rather than with IL-1β. At 3 h after IL-1β treatment, 18 amino acids (except cysteine and glutamic acid), total glutathione (GSH, GSSG, Cys-GSH disulfide), Met-sulfoxide, 5-oxoproline, and SAM declined, whereas DNA expressions of AKT, CASP3, and CXCL3 were elevated. These changes were reversed by simultaneous treatment with SE. The present study suggests that the anti-inflammatory action of SE is mediated via various metabolic pathways for cell survival, apoptosis, and leukocyte recruitment.

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Membrane traffic related to endosome dynamics and protein secretion in filamentous fungi

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab004 ◽

2021 ◽

Author(s):

Yujiro Higuchi

Keyword(s):

Filamentous Fungi ◽

Protein Secretion ◽

Secretory Pathway ◽

Molecular Mechanisms ◽

Membrane Traffic ◽

Early Endosome ◽

Protein Glycosylation ◽

Hyphal Cell ◽

Cell Factories ◽

Membrane Contacts

ABSTRACT In eukaryotic cells, membrane-surrounded organelles are orchestrally organized spatiotemporally under environmental situations. Among such organelles, vesicular transports and membrane contacts occur to communicate each other, so-called membrane traffic. Filamentous fungal cells are highly polarized and thus membrane traffic is developed to have versatile functions. Early endosome (EE) is an endocytic organelle that dynamically exhibits constant long-range motility through the hyphal cell, which is proven to have physiological roles, such as other organelle distribution and signal transduction. Since filamentous fungal cells are also considered as cell factories, to produce valuable proteins extracellularly, molecular mechanisms of secretory pathway including protein glycosylation have been well investigated. In this review, molecular and physiological aspects of membrane traffic especially related to EE dynamics and protein secretion in filamentous fungi are summarized, and perspectives for application are also described.

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Molecular characterization of HEK293 cells as emerging versatile cell factories

Current Opinion in Biotechnology ◽

10.1016/j.copbio.2021.05.001 ◽

2021 ◽

Vol 71 ◽

pp. 18-24

Author(s):

Michela Pulix ◽

Vera Lukashchuk ◽

Daniel C Smith ◽

Alan J Dickson

Keyword(s):

Molecular Characterization ◽

Hek293 Cells ◽

Cell Factories

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Multiple 'omics'-analysis reveals the role of prostaglandin E2 in Hirschsprung's disease

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2020.12.456 ◽

2021 ◽

Vol 164 ◽

pp. 390-398

Author(s):

Weibing Tang ◽

Minjian Chen ◽

Xuejiang Guo ◽

Kun Zhou ◽

Zechao Wen ◽

...

Keyword(s):

Prostaglandin E2 ◽

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Omics Analysis

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Enzymatic Hydrolysate of Cinnamon Waste Material as Feedstock for the Microbial Production of Carotenoids

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18031146 ◽

2021 ◽

Vol 18 (3) ◽

pp. 1146

Author(s):

Stefano Bertacchi ◽

Stefania Pagliari ◽

Chiara Cantù ◽

Ilaria Bruni ◽

Massimo Labra ◽

...

Keyword(s):

Industrial Sector ◽

Waste Material ◽

Fungal Cell ◽

Enzymatic Hydrolysate ◽

Carbon And Nitrogen ◽

Microbial Cell Factories ◽

Cell Factories ◽

Separate Hydrolysis And Fermentation ◽

Additional Processing ◽

Microbial Cultivation

In the context of the global need to move towards circular economies, microbial cell factories can be employed thanks to their ability to use side-stream biomasses from the agro-industrial sector to obtain additional products. The valorization of residues allows for better and complete use of natural resources and, at the same time, for the avoidance of waste management to address our needs. In this work, we focused our attention on the microbial valorization of cinnamon waste material after polyphenol extraction (C-PEW) (Cinnamomum verum J.Presl), generally discarded without any additional processing. The sugars embedded in C-PEW were released by enzymatic hydrolysis, more compatible than acid hydrolysis with the subsequent microbial cultivation. We demonstrated that the yeast Rhodosporidium toruloides was able to grow and produce up to 2.00 (±0.23) mg/L of carotenoids in the resulting hydrolysate as a sole carbon and nitrogen source despite the presence of antimicrobial compounds typical of cinnamon. To further extend the potential of our finding, we tested other fungal cell factories for growth on the same media. Overall, these results are opening the possibility to develop separate hydrolysis and fermentation (SHF) bioprocesses based on C-PEW and microbial biotransformation to obtain high-value molecules.

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