Metabolic engineering of carbon and redox flow in the production of small organic acids

Thakker, Chandresh; Martínez, Irene; Li, Wei; San, Ka‐Yiu; Bennett, George N.

doi:10.1007/s10295-014-1560-y

Cited by 52 publications

(25 citation statements)

References 227 publications

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“…120 Fumaric acid, a 4-carbon dicarboxylic acid, is made by species of Rhizopus at levels of 126-130 g l − 1 . 121 Rhizopus arrhizus has been utilized by the Pfizer corporation to make 4000 tons per year. 122 DuPont patented a process using R. arrhizus NRRL-1526 with limited dissolved oxygen to produce 130 g l − 1 .…”

Section: Organic Acidsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian's areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian's accomplishments to continue into the future.

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Section: Organic Acidsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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“…Clostridium beijerinckii , a spore‐forming, solventogenic, Gram‐positive bacterium, is a potentially important industrial strain as it can utilize a variety of carbon‐based feedstock to generate valuable chemicals and fuels (Chen & Blaschek, ; Dürre, ; Ezeji, Qureshi, & Blaschek, ; Y. Gu, Jiang, Yang, & Jiang, ; Jiang, Liu, Jiang, Yang, & Yang, ; Lee et al, ; Thakker, Martínez, Li, San, & Bennett, ). The establishment of convenient to use, effective gene tools with which the organism can be rapidly modified is essential if its full potential is to be realized.…”

Section: Introductionmentioning

confidence: 99%

CRISPR–Cas9^D10A nickase‐assisted base editing in the solvent producer Clostridium beijerinckii

Seys

Minton

et al. 2019

Biotech & Bioengineering

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Clostridium beijerinckii is a potentially important industrial microorganism as it can synthesize valuable chemicals and fuels from various carbon sources. The establishment of convenient to use, effective gene tools with which the organism can be rapidly modified is essential if its full potential is to be realized. Here, we developed a genomic editing tool (pCBEclos) for use in C. beijerinckii based on the fusion of cytidine deaminase (Apobec1), Cas9 D10A nickase and uracil DNA glycosylase inhibitor (UGI). Apobec1 and UGI are guided to the target site where they introduce specific base-pair substitutions through the conversion of C·G to T·A. By appropriate choice of target sequence, these nucleotide changes are capable of creating missense mutation or null mutations in a gene. Through optimization of pCBEclos, the system derived, pCBEclos-opt, has been used to rapidly generate four different mutants in C.beijerinckii, in pyrE, xylR, spo0A, and araR. The efficiency of the system was such that they could sometimes be directly obtained following transformation, otherwise only requiring one single restreaking step. Whilst CRISPR-Cas9 nickase systems, such as pNICKclos2.0, have previously been reported in C. beijerinckii, pCBEclos-opt does not rely on homologous recombination, a process that is intrinsically inefficient in clostridia such as C. beijerinckii. As a consequence, bulky editing templates do not need to be included in the knockout plasmids. This both reduces plasmid size and makes their construction simpler, for example, whereas the assembly of pNICK-clos2.0 requires six primers for the assembly of a typical knockout plasmid, pCBEclosopt requires just two primers. The pCBEclos-opt plasmid established here represents a powerful new tool for genome editing in C. beijerinckii, which should be readily applicable to other clostridial species.

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“…l ‐malate, an essential intermediate of cell metabolism, is widely used in food and beverage industry as an acidulant and taste enhancer (Thakker, Li, San, & Bennett, ). l ‐malate can also be used to treat hyperammonemia and liver dysfunction as a component of amino acid infusions (Battat, Peleg, Bercovitz, Rokem, & Goldberg, ).…”

Section: Introductionmentioning

confidence: 99%

Morphology engineering of Aspergillus oryzae for l‐malate production

Chen

Zhou

Ding

et al. 2019

Biotech & Bioengineering

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Aspergillus oryzae is a competitive natural producer for organic acids, but its production capacity is closely correlated with a specific morphological type. Here, morphology engineering was used for tailoring A. oryzae morphology to enhance L-malate production. Specifically, correlation between A. oryzae morphology and L-malate fermentation was first conducted, and the optimal range of the total volume of pellets in a unit volume of fermentation broth (V value) for L-malate production was 120-130 mm 3 /ml. To achieve this range, A. oryzae morphology was improved by controlling the variation of operational parameters, such as agitation speed and aeration rate, and engineered by optimizing the expression of cell division cycle proteins such as tyrosine-protein phosphatase (CDC14), anaphase promoting complex/cyclosome activator protein (CDC20), and cell division control protein 45 (CDC45). By controlling the strength of CDC14 at a medium level, V value fell into the optimal range of V value and the final engineered strain A. oryzae CDC14 (3) produced up to 142.5 g/L L-malate in a 30-L fermenter. This strategy described here lays a good foundation for industrial production of L-malate in the future, and opens a window to develop filamentous fungi as cell factories for production of other chemicals. K E Y W O R D SAspergillus oryzae, L-malate, metabolic engineering, morphology engineering

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Metabolic engineering of carbon and redox flow in the production of small organic acids

Cited by 52 publications

References 227 publications

Production of valuable compounds by molds and yeasts

Production of valuable compounds by molds and yeasts

CRISPR–Cas9^D10A nickase‐assisted base editing in the solvent producer Clostridium beijerinckii

Morphology engineering of Aspergillus oryzae for l‐malate production

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Metabolic engineering of carbon and redox flow in the production of small organic acids

Cited by 52 publications

References 227 publications

Production of valuable compounds by molds and yeasts

Production of valuable compounds by molds and yeasts

CRISPR–Cas9D10A nickase‐assisted base editing in the solvent producer Clostridium beijerinckii

Morphology engineering of Aspergillus oryzae for l‐malate production

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Product

Resources

About

CRISPR–Cas9^D10A nickase‐assisted base editing in the solvent producer Clostridium beijerinckii