Metabolic engineering and synthetic biology approaches driving isoprenoid production in Escherichia coli

Wang, Chonglong; Zada, Bakht; Wei, Gongyuan; Kim, Seon-Won

doi:10.1016/j.biortech.2017.05.168

Cited by 70 publications

(43 citation statements)

References 98 publications

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“…Acetyl‐CoA is involved in various biological processes and it serves as a platform chemical for producing various high‐value products, such as 1‐butanol (Dong et al, 2017; Ohtake et al, 2017), 3‐hydroxypropionate (Cheng, Jiang, Wu, Li, & Ye, 2016; Liu et al, 2017), polyhydroxyalkanoates (Zheng, Yuan, Yang, & Ma, 2017) and isoprenoids. Isoprenoids may be used for flavorings, biofuels, pharmaceuticals, vitamins (Wang, Zada, Wei, & Kim, 2017; Ward, Chatzivasileiou, & Stephanopoulos, 2018). Acetyl‐CoA is the most important precursor for mevalonate production.…”

Section: Discussionmentioning

confidence: 99%

Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl‐CoA supply

Satowa

Fujiwara

Uchio

et al. 2020

Biotech & Bioengineering

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Microbial production of mevalonate from renewable feedstock is a promising and sustainable approach for the production of value‐added chemicals. We describe the metabolic engineering of Escherichia coli to enhance mevalonate production from glucose and cellobiose. First, the mevalonate‐producing pathway was introduced into E. coli and the expression of the gene atoB, which encodes the gene for acetoacetyl‐CoA synthetase, was increased. Then, the deletion of the pgi gene, which encodes phosphoglucose isomerase, increased the NADPH/NADP+ ratio in the cells but did not improve mevalonate production. Alternatively, to reduce flux toward the tricarboxylic acid cycle, gltA, which encodes citrate synthetase, was disrupted. The resultant strain, MGΔgltA‐MV, increased levels of intracellular acetyl‐CoA up to sevenfold higher than the wild‐type strain. This strain produced 8.0 g/L of mevalonate from 20 g/L of glucose. We also engineered the sugar supply by displaying β‐glucosidase (BGL) on the cell surface. When cellobiose was used as carbon source, the strain lacking gnd displaying BGL efficiently consumed cellobiose and produced mevalonate at 5.7 g/L. The yield of mevalonate was 0.25 g/g glucose (1 g of cellobiose corresponds to 1.1 g of glucose). These results demonstrate the feasibility of producing mevalonate from cellobiose or cellooligosaccharides using an engineered E. coli strain.

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Section: Discussionmentioning

confidence: 99%

Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl‐CoA supply

Satowa

Fujiwara

Uchio

et al. 2020

Biotech & Bioengineering

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“…Currently, the plant terpenoid bisabolene has a wide range of applications in cosmetic, chemical, pharmaceutical and nutraceutical industries [1,2]. Traditionally, bisabolene is extensively used as a high-value fragrance and avour compound in many industries because bisabolene has highly pleasant fruity and balsamic aroma [3]. For example, β-bisabolene has an odor similar to sesame oil and thus can be used as a food avoring.…”

Section: Introductionmentioning

confidence: 99%

High-Efficiency Production of the Bisabolene from Waste Cooking Oil By Metabolically Engineered Yarrowia Lipolytica

Zhao

Zhu

et al. 2020

Preprint

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Background: The natural plant product bisabolene serves as a precursor for the production of a wide range of industrially relevant chemicals. However, the low abundance of bisabolene in plants renders their isolation from plant sources economically inviable. Therefore, creation of microbial cell factories for bisabolene production supported by synthetic biology and metabolic engineering strategies presents a more competitive and environmentally sustainable method for industrial production of bisabolene.Results: In this proof-of-principle study, for the first time, we engineered the oleaginous yeast Yarrowia lipolytica to produce α-bisabolene, β-bisabolene and γ-bisabolene through heterologous expression of the α-bisabolene synthase from Abies grandis, the β-bisabolene synthase gene from Zingiber officinale and the γ-bisabolene synthase gene from Helianthus annuus, respectively. Subsequently, metabolic engineering approaches, including overexpression of the endogenous mevalonate pathway genes and introduction of heterologous multidrug efflux transporters, were employed to improve bisabolene production. Furthermore, the fermentation conditions were optimized to maximize de novo bisabolene production by the engineered Y. lipolytica strains from glucose. Our engineering strategies have led to engineered Y. lipolytica strains that produce 282.6 mg/L α-bisabolene, 48.3 mg/L β-bisabolene and 5.3 mg/L γ-bisabolene. Finally, we explored the potential of the engineered Y. lipolytica strains for bisabolene production from waste cooking oil. The results showed that α-bisabolene, β-bisabolene and γ-bisabolene could be produced at the respective titers of 973.0 mg/L, 68.2 mg/L, 20.2 mg/L in shake flasks. These titers correspond to 2433-fold, 340-fold and 404-fold enhancement in bisabolene production, respectively, over the parent strain.Conclusions: To our knowledge, this is the first report of bisabolene production in Y. lipolytica. These findings provide valuable insights into the engineering of Y. lipolytica for higher-level production of bisabolene and its utilization in converting waste cooking oil into various industrially valuable products.

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“…gas-to-liquid bioconversion using methanotrophs, such as limited mass transfer rates of methane, low volumetric productivity, and instability of recombinant strains [11].Secondary metabolites produced by plants and microorganisms have many useful biological activities. Among the many secondary metabolites, isoprenoids are the largest family of natural products, with more than 50,000 members identified [12][13][14]. Many isoprenoids have been used in many applications such as pharmaceuticals, nutraceuticals, fragrances, as well as the chemical industry.…”

mentioning

confidence: 99%

“…Plants are the major sources of isoprenoids. However, there are still many limitations for the production of high quantities of natural isoprenoids, including slow growth and tissue-specific biosynthesis, and difficulties in harvesting and extraction [12][13][14]. In contrast, a promising alternative method for isoprenoid production is the reconstruction of isoprenoid biosynthesis pathways from plants into microbes.…”

mentioning

confidence: 99%

“…In contrast, a promising alternative method for isoprenoid production is the reconstruction of isoprenoid biosynthesis pathways from plants into microbes. The application of this approach has been extensively studied on model organisms like Escherichia coli or Saccharomyces cerevisiae for a variety of isoprenoids [12,14]. E. coli and S. cerevisiae are promising hosts since they possess simple genetic backgrounds, high growth rates as well as well-developed genetic tools.…”

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confidence: 99%

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Bioproduction of Isoprenoids and Other Secondary Metabolites Using Methanotrophic Bacteria as an Alternative Microbial Cell Factory Option: Current Stage and Future Aspects

2019

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Methane is a promising carbon feedstock for industrial biomanufacturing because of its low price and high abundance. Recent advances in metabolic engineering and systems biology in methanotrophs have made it possible to produce a variety of value-added compounds from methane, including secondary metabolites. Isoprenoids are one of the largest family of secondary metabolites and have many useful industrial applications. In this review, we highlight the current efforts invested to methanotrophs for the production of isoprenoids and other secondary metabolites, including riboflavin and ectoine. The future outlook for improving secondary metabolites production (especially of isoprenoids) using metabolic engineering of methanotrophs is also discussed. gas-to-liquid bioconversion using methanotrophs, such as limited mass transfer rates of methane, low volumetric productivity, and instability of recombinant strains [11].Secondary metabolites produced by plants and microorganisms have many useful biological activities. Among the many secondary metabolites, isoprenoids are the largest family of natural products, with more than 50,000 members identified [12][13][14]. Many isoprenoids have been used in many applications such as pharmaceuticals, nutraceuticals, fragrances, as well as the chemical industry. Additionally, due to the methyl-branched and cyclized hydrocarbon alkene structure, some isoprenoids have attracted more attention for their potential use as advanced biofuels. Plants are the major sources of isoprenoids. However, there are still many limitations for the production of high quantities of natural isoprenoids, including slow growth and tissue-specific biosynthesis, and difficulties in harvesting and extraction [12][13][14]. In contrast, a promising alternative method for isoprenoid production is the reconstruction of isoprenoid biosynthesis pathways from plants into microbes. The application of this approach has been extensively studied on model organisms like Escherichia coli or Saccharomyces cerevisiae for a variety of isoprenoids [12,14]. E. coli and S. cerevisiae are promising hosts since they possess simple genetic backgrounds, high growth rates as well as well-developed genetic tools. For example, high production of isoprenoid-based biofuels has been achieved in the metabolic engineering of microbes via endogenous or heterologous biosynthetic pathways in these hosts. However, the vast majority of these microbe-based isoprenoid production cases rely on sugar-based metabolism, which is likely to increase in the price of isoprenoids produced in large quantity.The use of alternative carbon sources is attractive in industrial biotechnology for isoprenoid production. Furthermore, different type of pathway regulation in different microbes utilizing unusual carbon substrate like methane can play a vital role in metabolic engineering of various microbes including model organisms. Thus, metabolic engineering of methane-utilizing methanotrophs has recently attracted much attention, due to not only cheaper price of...

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Metabolic engineering and synthetic biology approaches driving isoprenoid production in Escherichia coli

Cited by 70 publications

References 98 publications

Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl‐CoA supply

Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl‐CoA supply

High-Efficiency Production of the Bisabolene from Waste Cooking Oil By Metabolically Engineered Yarrowia Lipolytica

Bioproduction of Isoprenoids and Other Secondary Metabolites Using Methanotrophic Bacteria as an Alternative Microbial Cell Factory Option: Current Stage and Future Aspects

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