Recent Advances in Microbial Cell Growth Regulation Strategies for Metabolic Engineering

Noh, Myung Hyun; Cha, Sanghak; Kim, Min-Sun; Jung, Gyoo Yeol

doi:10.1007/s12257-019-0511-x

Cited by 16 publications

(11 citation statements)

References 147 publications

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“…Algal astaxanthin synthesis is usually induced as a defense mechanism against environmental oxidative stress [2,5,6]. Various stress-inducing conditions, such as nutrient starvation [7,8], exposure to intense light [9,10], high temperatures [11,12], high salinity [13,14], and nanomaterial addition to culture [15], have been applied to increase the content and productivity of algal astaxanthin.…”

Section: Introductionmentioning

confidence: 99%

Electric Stimulation of Astaxanthin Biosynthesis in Haematococcus pluvialis

et al. 2021

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The green microalga Haematococcus pluvialis accumulates astaxanthin, a potent antioxidant pigment, as a defense mechanism against environmental stresses. In this study, we investigated the technical feasibility of a stress-based method for inducing astaxanthin biosynthesis in H. pluvialis using electric stimulation in a two-chamber bioelectrochemical system. When a cathodic (reduction) current of 3 mA (voltage: 2 V) was applied to H. pluvialis cells for two days, considerable lysis and breakage of algal cells were observed, possibly owing to the formation of excess reactive oxygen species at the cathode. Conversely, in the absence of cell breakage, the application of anodic (oxidation) current effectively stimulated astaxanthin biosynthesis at a voltage range of 2–6 V, whereas the same could not be induced in the untreated control. At an optimal voltage of 4 V (anodic current: 30 mA), the astaxanthin content in the cells electro-treated for 2 h was 36.9% higher than that in untreated cells. Our findings suggest that electric treatment can be used to improve astaxanthin production in H. pluvialis culture if bioelectrochemical parameters, such as electric strength and duration, are regulated properly.

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Section: Introductionmentioning

confidence: 99%

Electric Stimulation of Astaxanthin Biosynthesis in Haematococcus pluvialis

et al. 2021

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“…After the PrpD VTL mutant dominates during the initial enrichment, hitchhikers may have been enriched together through crosstalk effects 37 . Nonetheless, we screened for effective mutant in four rounds of enrichment and observed an unintended decrease in catalytic e ciency toward cis-aconitate, supporting the effectiveness of the high-throughput screening system 21,24,25,38,39 . This method can be further applied in diverse strategies for itaconate production, including adaptive laboratory evolution, the evolution of cis-aconitate decarboxylase, and even the de novo itaconate production pathway.…”

Section: Discussionmentioning

confidence: 56%

Kinetic compartmentalization by unnatural reaction for itaconate production

Daeyeol

Noh

Moon

et al. 2021

Preprint

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Physical compartmentalization of metabolisms using membranous organelles in eukaryotes is helpful for chemical biosynthesis to ensure the availability of substrates from competitive metabolic reactions. Bacterial hosts lack such a membranous system, which is one of the major limitations for efficient metabolic engineering. Here, we introduced kinetic compartmentalization as an alternative strategy to enable substrate availability from competitive reactions. This method utilizes a non-natural biochemical reaction performed by an engineered enzyme to kinetically isolate the metabolic pathways and ensure substrate availability for the desired reaction. As a proof of concept, we could successfully demonstrate kinetic separation for efficient itaconate production from acetate in Escherichia coli, mimicking the native mitochondrial membrane system in Aspergillus species. Despite the utilization of the non-preferred carbon source, kinetic compartmentalization could lead to substantial increases of itaconate in both yield and titer, suggesting enough potential of our strategy for broad applications in diverse engineering.

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“…glutamicum and concentration of total squalene in the top layer without cell disruption. Further, an active secretion by expressing a transporter protein in engineered strain will significantly increase the production, and decoupling the production from the cell growth will increase the production yield . Thus, this study showed that it is feasible to take advantage of engineered C.…”

Section: Discussionmentioning

confidence: 79%

Microbial Bioprocess for Extracellular Squalene Production and Formulation of Nanoemulsions

Park

Kang

Woo

2021

ACS Sustainable Chem. Eng.

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Sustainable production of natural resources requires a clean manufacturing process with clean raw materials due to the risk of environmental contaminations. Microbial cell factories have enabled the production of natural products including hydrophobic chemicals. However, the microbial cells limit the production titer because of the limited intracellular storage capacity and no transport across the cell membrane. Herein, we engineered Corynebacterium glutamicum to produce hydrophobic squalene as a model product. Notably, squalene was secreted in the defined culture medium without in situ extractions. As a result, the secreted squalene was related to the glycolipid association with synthesized squalene in the cell envelope and a facilitated secretion occurred during cell division. Protein engineering and pathway engineering of C. glutamicum enhanced the total squalene (tSQ) production, where fed-batch fermentation resulted in 1406 ± 16 mg/L tSQ production (32% tSQ in the medium). Promoting extraction with dodecane overlay, bio-squalene nanoemulsions were formulated and the creaming effects were analyzed for cosmetic application. Combining metabolic pathway engineering and facilitated secretion in microbial cells will be a good strategy to produce sustainable hydrophobic chemicals.

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Recent Advances in Microbial Cell Growth Regulation Strategies for Metabolic Engineering

Cited by 16 publications

References 147 publications

Electric Stimulation of Astaxanthin Biosynthesis in Haematococcus pluvialis

Electric Stimulation of Astaxanthin Biosynthesis in Haematococcus pluvialis

Kinetic compartmentalization by unnatural reaction for itaconate production

Microbial Bioprocess for Extracellular Squalene Production and Formulation of Nanoemulsions

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