Development of bio-based fine chemical production through synthetic bioengineering

Hara, Kiyotaka Y.; Araki, Michihiro; Okai, Naoko; Wakai, Satoshi; Hasunuma, Tomohisa; Kondo, Akihiko

doi:10.1186/preaccept-1199106075136638

Cited by 7 publications

(11 citation statements)

References 79 publications

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“…The high value of glutathione in industry has led to many studies being conducted, mainly in S. cerevisiae, to improve production by optimizing culture conditions and metabolic engineering, as S. cerevisiae is the main microorganism presently used for industrial glutathione production (Li et al 2004;Hara et al 2014). However, in most of these previous studies, the glutathione content was increased as GSH because most intracellular glutathione molecules exist as GSH due to the glutathione redox metabolism.…”

Section: Discussionmentioning

confidence: 96%

“…This glutathione redox metabolism involves both oxidization of GSH to GSSG by glutathione peroxidases, glutathione S-transferase, or free radicals and reduction of GSSG to GSH by glutathione reductase (Pócsi et al 2004). Many studies have been carried out to increase glutathione production using S. cerevisiae (Li et al 2004;Hara et al 2014). Overexpression of GSH1 and GSH2 increased the intracellular glutathione content in S. cerevisiae (Hara et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae

Hara

Aoki

Kobayashi

et al. 2015

Appl Microbiol Biotechnol

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Glutathione is a valuable tripeptide widely used in the pharmaceutical, food, and cosmetic industries. In industrial fermentation, glutathione is currently produced primarily using the yeast Saccharomyces cerevisiae. Intracellular glutathione exists in two forms; the majority is present as reduced glutathione (GSH) and a small amount is present as oxidized glutathione (GSSG). However, GSSG is more stable than GSH and is a more attractive form for the storage of glutathione extracted from yeast cells after fermentation. In this study, intracellular GSSG content was improved by engineering thiol oxidization metabolism in yeast. An engineered strain producing high amounts of glutathione from over-expression of glutathione synthases and lacking glutathione reductase was used as a platform strain. Additional over-expression of thiol oxidase (1.8.3.2) genes ERV1 or ERO1 increased the GSSG content by 2.9-fold and 2.0-fold, respectively, compared with the platform strain, without decreasing cell growth. However, over-expression of thiol oxidase gene ERV2 showed almost no effect on the GSSG content. Interestingly, ERO1 over-expression did not decrease the GSH content, raising the total glutathione content of the cell, but ERV1 over-expression decreased the GSH content, balancing the increase in the GSSG content. Furthermore, the increase in the GSSG content due to ERO1 over-expression was enhanced by additional over-expression of the gene encoding Pdi1, whose reduced form activates Ero1 in the endoplasmic reticulum. These results indicate that engineering the thiol redox metabolism of S. cerevisiae improves GSSG and is critical to increasing the total productivity and stability of glutathione.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae

Hara

Aoki

Kobayashi

et al. 2015

Appl Microbiol Biotechnol

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“…Furthermore, the use of microbial hosts for the production of polyphenols simplifies the product purification procedure, as their secondary metabolism is generally much simpler and competing pathways can be eliminated or deactivated. Lastly, as opposed to the traditional methods for obtaining natural products, microbial-based production can be a lot more environmentally-friendly, as the use of organic solvents or other harsh chemicals for product purification can be reduced [85,86]. Production of fine chemicals 8 using microorganisms also requires considerably less natural resources, such as extensive land and water usage, as well as fertilizers and pesticides, needed to obtain and process large amounts of raw plant material [87,88].…”

Section: Microbial Production Of Plant Polyphenols: Past Achievementsmentioning

confidence: 99%

Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties

Dudnik

Gaspar

Neves

et al. 2018

CPD

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Polyphenols form a group of important natural bioactive compounds with numerous ascribed healthbeneficial attributes (e.g. antioxidant, anti-inflammatory, anti-microbial and tumor-suppressing properties). Some polyphenols can also be used as natural dyes or plastic precursors. Notwithstanding their relevance, production of most of these compounds still relies on extraction from plant material, which for most of it is a costly and an inefficient procedure. The use of microbial cell factories for this purpose is an emerging alternative that could allow a more efficient and sustainable production. The most recent advances in molecular biology and genetic engineering, combined with the ever-growing understanding of microbial physiology have led to multiple success stories. Production of multiple polyphenolic compounds or their direct precursors has been achieved not only in the common production hosts, such as Escherichia coli and Saccharomyces cerevisiae, but also in Corynebacterium glutamicum and Lactococcus lactis. However, boosting production of native compounds or introduction of heterologous biosynthetic pathways also brings certain challenges, such as the need to express, balance and maintain efficient precursor supply. This review will discuss the most recent advances in the field of metabolic engineering of microorganisms for polyphenol biosynthesis and its future perspectives, as well as outlines their potential health benefits and current production methods.

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“…Synthetic biology techniques that insert standardized and characterized genetic parts are used to regulate and fine‐tuning the engineered biosynthetic pathways in the chassis (Chao et al ., ). Nowadays, the establishment of synthetic biology bio‐foundries enables the application of automated design–build–test–learn cycles to microbial cell factories so that natural pathways can be refactored and novel reactions and products can be discovered (Hara et al ., ; Carbonell et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Mapping the patent landscape of synthetic biology for fine chemical production pathways

Carbonell

Gök

Shapira

et al. 2016

Microbial Biotechnology

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SummaryA goal of synthetic biology bio‐foundries is to innovate through an iterative design/build/test/learn pipeline. In assessing the value of new chemical production routes, the intellectual property (IP) novelty of the pathway is important. Exploratory studies can be carried using knowledge of the patent/IP landscape for synthetic biology and metabolic engineering. In this paper, we perform an assessment of pathways as potential targets for chemical production across the full catalogue of reachable chemicals in the extended metabolic space of chassis organisms, as computed by the retrosynthesis‐based algorithm RetroPath. Our database for reactions processed by sequences in heterologous pathways was screened against the PatSeq database, a comprehensive collection of more than 150M sequences present in patent grants and applications. We also examine related patent families using Derwent Innovations. This large‐scale computational study provides useful insights into the IP landscape of synthetic biology for fine and specialty chemicals production.

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Development of bio-based fine chemical production through synthetic bioengineering

Cited by 7 publications

References 79 publications

Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae

Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae

Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties

Mapping the patent landscape of synthetic biology for fine chemical production pathways

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