A single-host fermentation process for the production of flavor lactones from non-hydroxylated fatty acids

Marella, Eko Roy; Dahlin, Jonathan; Dam, Marie Inger; Horst, Jolanda ter; Christensen, Hanne Bjerre; Sudarsan, Suresh; Wang, Guokun; Holkenbrink, Carina; Borodina, Irina

doi:10.1016/j.ymben.2019.08.009

Cited by 62 publications

(54 citation statements)

References 49 publications

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“…Moreover, Y. lipolytica lacks efficient endogenous enzymes for utilization of sucrose or starch [39,40]. On the other hand, while 1 mol of oleic acid could yield a maximum of 9 mol of acetyl-CoA, in Y. lipolytica oleic acid appears to be utilized more for lipid accumulation [41].…”

Section: High-level Production Of β-Ionone In Fed-batch Fermentationmentioning

confidence: 99%

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Yang

Lin

et al. 2020

Microb Cell Fact

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Background: The GRAS and oleaginous yeast Yarrowia lipolytica (Y. lipolytica) is an attractive cell factory for the production of chemicals and biofuels. The production of many natural products of commercial interest have been investigated in this cell factory by introducing heterologous biosynthetic pathways and by modifying the endogenous pathways. However, since natural products anabolism involves long pathways and complex regulation, re-channelling carbon into the product of target compounds is still a cumbersome work, and often resulting in low production performance. Results: In this work, the carotenogenic genes contained carB and bi-functional carRP from Mucor circinelloides and carotenoid cleavage dioxygenase 1 (CCD1) from Petunia hybrida were introduced to Y. lipolytica and led to the low production of β-ionone of 3.5 mg/L. To further improve the β-ionone synthesis, we implemented a modular engineering strategy for the construction and optimization of a biosynthetic pathway for the overproduction of β-ionone in Y. lipolytica. The strategy involved the enhancement of the cytosolic acetyl-CoA supply and the increase of MVA pathway flux, yielding a β-ionone titer of 358 mg/L in shake-flask fermentation and approximately 1 g/L (~ 280-fold higher than the baseline strain) in fed-batch fermentation. Conclusions: An efficient β-ionone producing GRAS Y. lipolytica platform was constructed by combining integrated overexpressed of heterologous and native genes. A modular engineering strategy involved the optimization pathway and fermentation condition was investigated in the engineered strain and the highest β-ionone titer reported to date by a cell factory was achieved. This effective strategy can be adapted to enhance the biosynthesis of other terpenoids in Y. lipolytica.

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Section: High-level Production Of β-Ionone In Fed-batch Fermentationmentioning

confidence: 99%

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Yang

Lin

et al. 2020

Microb Cell Fact

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“…All strains in this study (see Table 1) are derived from the Yarrowia lipolytica strain ST6512 [14]. ST6512 is in turn derived from the W29 background strain (Y-63746 from the ARS Culture Collection, Peoria, USA; a.k.a.…”

Section: Strains and Strain Constructionmentioning

confidence: 99%

Deletion of MHY1 abolishes hyphae formation in Yarrowia lipolytica without negative effects on stress tolerance

Konzock¹,

Norbeck²

2020

PLoS ONE

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There is a need for development of sustainable production processes for production of fats/ oils and lipid derived chemicals. The dimorphic oleaginous yeast Yarrowia lipolytica is a promising organism for conversion of biomass hydrolysate to lipids, but in many such processes hyphae formation will be problematic. We have therefore constructed and compared the performance of strains carrying deletions in several published gene targets suggested to abolish hyphae formation (MHY1, HOY1 and CLA4). The MHY1-deletion was the only of the tested strains which did not exhibit hyphae formation under any of the conditions tested. The MHY1-deletion also had a weak positive effect on lipid accumulation without affecting the total fatty acid composition, irrespective of the nitrogen source used. MHY1 has been suggested to constitute a functional homolog of the stress responsive transcription factors MSN2/4 in Saccharomyces cerevisiae, the deletion of which are highly stress sensitive. However, the deletion of MHY1 displayed only minor difference on survival of a range of acute or long term stress and starvation conditions. We conclude that the deletion of MHY1 in Y.lipolytica is a reliable way of abolishing hyphae formation with few detectable negative side effects regarding growth, stress tolerance and lipid accumulation and composition.

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“…Additionally, accumulation of delta-decalactone was obtained when the yeasts Lindnera saturnus CCMA 0243 and Yarrownia lipolytica CCMA 0242 were grown in residual castor oil (De Andrade et al, 2017). Recently, Marella et al (2019) engineered oleaginous yeast Yarrowia lipolytica for hydroxylation of fatty acids and chain-shortening via β-oxidation to preferentially 12 or 10 carbons. The engineered strains were found to produce 4-fold higher concentrations of γdodecalactone from oleic acid and δ-decalactone from linoleic acid than the wild strain, thereby paving the way for the higher production of lactones by fermentation of available fatty feedstocks.…”

Section: Lactonesmentioning

confidence: 99%

Prospecting the Potential of Agroresidues as Substrate for Microbial Flavor Production

Sharma

Singh

et al. 2020

Front. Sustain. Food Syst.

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With the growing consumer demand for natural food products, including food flavors, efforts toward identifying biotechnological interventions for their production have increased tremendously. The present paper reviews the production of flavor compounds by microbial biosynthesis or biotransformation, and their enzymes involved in synthesis and conversion from progenitor substrates. More importantly, the use of abundant, inexpensive, and nutrient-rich lignocellulosic waste generated by the processing setups of agro-industries as a potential substrate for the microbial production of flavor compounds under solid-state fermentation is reviewed. The article provides insights regarding the development of an efficient and cost-effective process to produce important flavors from agroresidues. The biotechnological route will also help in safe and eco-friendly management of wastes generated from agriculture.

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A single-host fermentation process for the production of flavor lactones from non-hydroxylated fatty acids

Cited by 62 publications

References 49 publications

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Deletion of MHY1 abolishes hyphae formation in Yarrowia lipolytica without negative effects on stress tolerance

Prospecting the Potential of Agroresidues as Substrate for Microbial Flavor Production

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