Engineering propionyl-CoA pools for
            <i>de novo</i>
            biosynthesis of odd-chain fatty acids in microbial cell factories

Qiao, Weibo; Dong, Genlai; Xu, Shijie; Li, Lingyun; Shi, Shuobo

doi:10.1080/07388551.2022.2100736

Cited by 7 publications

(11 citation statements)

References 63 publications

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“…By combining them, we proposed and confirmed a novel synthetic pathway for de novo OCFAs production from glucose (Figure 1), avoiding the use of propionate that added additional cost. This pathway showed a theoretical yield at 2 mol propionyl‐CoA/mol glucose, with a similar yield in mole of carbon atoms compared to other reported pathways (Qiao et al, 2022). As a widely used model strain, S. cerevisiae has a well‐established reputation for metabolic engineering and has been reported as an efficient host for fatty acids production (Yu et al, 2018; Zhu et al, 2020).…”

Section: Introductionsupporting

confidence: 82%

“…Free fatty acid production was achieved at 33.4 g/L in engineered S. cerevisiae (Yu et al, 2018), even higher than the popularly used oleaginous yeast Y. lipolytica (10.4 g/L) (Ledesma‐Amaro et al, 2016), indicating its potential as an efficient OCFAs producer. Furthermore, there are many studies in the construction of efficient 3‐HP producers in S. cerevisiae (Borodina et al, 2015; Qiao et al, 2022; N. Qin et al, 2020), drawing on experiences learned when the yeast was engineered to produce OCFAs via 3‐HP. For these reasons, S. cerevisiae was chosen as the host to construct the proposed pathway, which is also the first attempt for de novo OCFAs production from glucose in S. cerevisiae .…”

Section: Introductionmentioning

confidence: 99%

“…Despite progress already made in the bio‐production of OCFAs using precursor supplementation, limitations still exist that prevent its use in industrial scale applications. For example, the supplementation could lead to increased fermentation cost, and the addition of these chemicals showed direct or indirect toxic effects on cell growth (Qiao et al, 2022). Recently, an extended threonine biosynthesis pathway (named the aspartate/α‐ketobutyrate pathway) has been introduced to Y. lipolytica to provide propionyl‐CoA and realize the de novo production of OcFAs for the first time, which generated OCFAs at 0.36 g/L (5.64% of the total lipid) (Park et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…(Ledesma-Amaro et al, 2016), indicating its potential as an efficient OCFAs producer. Furthermore, there are many studies in the construction of efficient 3-HP producers in S. cerevisiae (Borodina et al, 2015;Qiao et al, 2022;N. Qin et al, 2020), drawing on experiences learned when the yeast was engineered to produce OCFAs via 3-HP.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, an extended threonine biosynthesis pathway (named the aspartate/α‐ketobutyrate pathway) has been introduced to Y. lipolytica to provide propionyl‐CoA and realize the de novo production of OcFAs for the first time, which generated OCFAs at 0.36 g/L (5.64% of the total lipid) (Park et al, 2020). In addition to this aspartate/α‐ketobutyrate pathway, several pathways have been proposed to make a de novo production of propionyl‐CoA and then OCFAs, and a recent review gave crucial perspectives to explore/evaluate/identify promising propionyl‐CoA biosynthetic pathways (Qiao et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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De novo bio‐production of odd‐chain fatty acids in Saccharomyces cerevisiae through a synthetic pathway via 3‐hydroxypropionic acid

Ding

Dong

et al. 2022

Biotech & Bioengineering

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Odd‐chain fatty acids (OCFAs) and their derivatives have attracted increasing attention due to their wide applications in the chemical, fuel, and pharmaceutical industry. However, most natural fatty acids are even‐chained, and OCFAs are rare. In this work, a novel pathway was designed and established for de novo synthesis of OCFAs via 3‐hydroxypropionic acid (3‐HP) as the intermediate in Saccharomyces cerevisiae. First, the OCFAs biosynthesis pathway from 3‐HP was confirmed, followed by an optimization of the precursor 3‐HP. After combining these strategies, a de novo production of OCFAs at 74.8 mg/L was achieved, and the percentage of OCFAs in total lipids reached 20.3%, reaching the highest ratio of de novo‐produced OCFAs. Of the OCFAs produced by the engineered strain, heptadecenoic acid (C17:1) and heptadecanoic acid (C17:0) accounted for 12.1% and 7.6% in total lipid content, respectively. This work provides a new and promising pathway for the de novo bio‐production of OCFAs.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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De novo bio‐production of odd‐chain fatty acids in Saccharomyces cerevisiae through a synthetic pathway via 3‐hydroxypropionic acid

Ding

Dong

et al. 2022

Biotech & Bioengineering

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Enhancing the biomass and docosahexaenoic acid‐rich lipid accumulation of Schizochytrium sp. in propionate wastewater

Zhang

et al. 2023

Biotechnology Journal

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In order to find a more effective way to obtain docosahexaenoic acid (DHA) rich lipid from Schizochytrium sp., a widespread propionate wastewater (PW) is used. PW is a common industrial and domestic wastewater, and transforming it into valuable products is a potential treatment method. Schizochytrium sp. is a rapidly growing oleaginous organism, which has been used commercially for DHA production. Herein, PW is completely used for DHA production by Schizochytrium sp. by genetic engineering and fermentation optimization, which can alleviate the increasingly tense demand for water resources and environmental pollution caused by industrial wastewater. Firstly, the methylmalonyl‐CoA mutase (MCM) was overexpressed in Schizochytrium sp. to enhance the metabolism of propionate, then the engineered strain of overexpressed MCM (OMCM) can effectively use propionate. Then, the effects of PW with different concentration of propionate were investigated, and results showed that OMCM can completely replace clean water with PW containing 5 g L−1 propionate. Furthermore, in the fed‐batch fermentation, the OMCM obtained the highest biomass of 113.4 g L−1 and lipid yield of 64.4 g L−1 in PW condition, which is 26.8% and 51.7% higher than that of wild type (WT) in PW condition. Moreover, to verify why overexpression of MCM can promote DHA and lipid accumulation, the comparative metabolomics, ATP production level, the antioxidant system, and the transcription of key genes were investigated. Results showed that ATP induced by PW condition could drive the synthesis of DHA, and remarkably improve the antioxidant capacity of cells by enhancing the carotenoids production. Therefore, PW can be used as an effective and economical substrate and water source for Schizochytrium sp. to accumulate biomass and DHA.

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Advances in biosynthesis of higher alcohols in Escherichia coli

Huang

2023

World J Microbiol Biotechnol

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Engineering propionyl-CoA pools for de novo biosynthesis of odd-chain fatty acids in microbial cell factories

Cited by 7 publications

References 63 publications

De novo bio‐production of odd‐chain fatty acids in Saccharomyces cerevisiae through a synthetic pathway via 3‐hydroxypropionic acid

De novo bio‐production of odd‐chain fatty acids in Saccharomyces cerevisiae through a synthetic pathway via 3‐hydroxypropionic acid

Enhancing the biomass and docosahexaenoic acid‐rich lipid accumulation of Schizochytrium sp. in propionate wastewater

Advances in biosynthesis of higher alcohols in Escherichia coli

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