Improvement of Stearidonic Acid Production in Oleaginous<i>Saccharomyces cerevisiae</i>

Kimura, Kouji; Tomita, Nao; Uemura, Hiroshi; Aki, Tsunehiro; Ono, Kazuhisa; Kamisaka, Yasushi

doi:10.1271/bbb.90082

Cited by 15 publications

(6 citation statements)

References 13 publications

(14 reference statements)

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“…Scientists are trying to construct engineered SDA-producing microbes because of nutritional value and increased demand. Kimura et al constructed genetically modified Saccharomyces cerevisiae which can produce up to 13% SDA when the fungus is supplied with increased histidine [36,37]. The recombinant M. circinelloides in this study can produce almost 5% SDA without any supplement and according to our knowledge, this is the first study describing the overexpression of D15D gene in M. circinelloides to construct SDA producing cell factory.…”

Section: Discussionmentioning

confidence: 77%

Genetic Modification of Mucor circinelloides to Construct Stearidonic Acid Producing Cell Factory

Khan

Yang

Hussain

et al. 2019

IJMS

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Stearidonic acid (SDA; 18:4, n-3) is the delta 15-desaturase product of gamma linolenic acid (GLA; 18:3, n-6) and delta 6-desaturase product of alpha linolenic acid (ALA; 18:3, n-3). Construction of engineered oleaginous microbes have been attracting significant interest in producing SDA because of its nutritional value and pharmaceutical applications. Mucor circinelloides is a GLA producing filamentous fungus, which can be a useful tool to produce SDA. This study has, therefore, overexpressed the delta-15 desaturase (D15D) gene from Mortierella alpina in this fungus to construct a SDA-producing cell factory. To produce SDA in M. circinelloides, the homologous overexpression of D15D gene was analyzed. When the gene was overexpressed in M. circinelloides CBS 277.49, up to 5.0% SDA was accumulated in this strain. According to current knowledge, this is the first study describing the construction of a SDA-producing cell factory by overexpression of D15D gene in oleaginous fungus M. circinelloides. A new scope for further research has been established by this work to improve SDA production in this fungus, specifically in its high lipid-producing strain, WJ11.

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Section: Discussionmentioning

confidence: 77%

Genetic Modification of Mucor circinelloides to Construct Stearidonic Acid Producing Cell Factory

Khan

Yang

Hussain

et al. 2019

IJMS

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“…Filtering out gene inducers, antibiotics or early precursors, we obtain a list of 8 curated pathways with supplementation (available as Supplementary Data S3). − In 5 cases out of 8, we retrieve the compound that was used for supplementation in the described experimental pathway. For 2 cases, we did not find the experimentally described supplement but suggest other possibilities.…”

Section: Resultsmentioning

confidence: 99%

“…We obtain a list of only 6 pathways satisfying these requirements, and 8 when we also add two pathways for TPA from literature . This list − is available as Supplementary Data S4.…”

Section: Methodsmentioning

confidence: 99%

Reinforcement Learning for Bioretrosynthesis

2019

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Metabolic engineering aims to produce chemicals of interest from living organisms, to advance towards greener chemistry. Despite efforts, the research and development process is still long and costly and efficient computational design tools are required to explore the chemical biosynthetic space. Here, we propose to explore the bio-retrosynthesis space using an Artificial Intelligence based approach relying on the Monte Carlo Tree Search reinforcement learning method, guided by chemical similarity. We implement this method in RetroPath RL, an open-source and modular command line tool. We validate it on a golden dataset of 20 manually curated experimental pathways as well as on a larger dataset of 152 successful metabolic engineering projects. Moreover, we provide a novel feature, that suggests potential media supplements to complement the enzymatic synthesis plan.

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“…To produce SDA, the delta-15 desaturase gene from Mortierella alpina was cloned and overexpressed in M. circinelloides CBS 277.49 , leading to the formation of 5% SDA of the total fatty acids [ 111 ]. 13% SDA can be produced by a genetically engineered Saccharomyces cerevisiae, when supplemented with histidne [ 112 , 113 ]. However engineered M. circinelloides strain produced SDA without any supplement.…”

Section: Metabolic Engineering Of M Circinelloides ...mentioning

confidence: 99%

Mucor circinelloides: a model organism for oleaginous fungi and its potential applications in bioactive lipid production

et al. 2022

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Microbial oils have gained massive attention because of their significant role in industrial applications. Currently plants and animals are the chief sources of medically and nutritionally important fatty acids. However, the ever-increasing global demand for polyunsaturated fatty acids (PUFAs) cannot be met by the existing sources. Therefore microbes, especially fungi, represent an important alternative source of microbial oils being investigated. Mucor circinelloides—an oleaginous filamentous fungus, came to the forefront because of its high efficiency in synthesizing and accumulating lipids, like γ-linolenic acid (GLA) in high quantity. Recently, mycelium of M. circinelloides has acquired substantial attraction towards it as it has been suggested as a convenient raw material source for the generation of biodiesel via lipid transformation. Although M. circinelloides accumulates lipids naturally, metabolic engineering is found to be important for substantial increase in their yields. Both modifications of existing pathways and re-formation of biosynthetic pathways in M. circinelloides have shown the potential to improve lipid levels. In this review, recent advances in various important metabolic aspects of M. circinelloides have been discussed. Furthermore, the potential applications of M. circinelloides in the fields of antioxidants, nutraceuticals, bioremediation, ethanol production, and carotenoids like beta carotene and astaxanthin having significant nutritional value are also deliberated.

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Improvement of Stearidonic Acid Production in OleaginousSaccharomyces cerevisiae

Cited by 15 publications

References 13 publications

Genetic Modification of Mucor circinelloides to Construct Stearidonic Acid Producing Cell Factory

Genetic Modification of Mucor circinelloides to Construct Stearidonic Acid Producing Cell Factory

Reinforcement Learning for Bioretrosynthesis

Mucor circinelloides: a model organism for oleaginous fungi and its potential applications in bioactive lipid production

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