Metabolic Engineering for Expanding the Substrate Range of  Yarrowia lipolytica

Ledesma-Amaro, Rodrigo

doi:10.1016/j.tibtech.2016.04.010

Cited by 189 publications

(108 citation statements)

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“…Yarrowia lipolytica is an oleaginous yeast widely investigated and modified for the production of biotechnologically relevant compounds (Ledesma‐Amaro & Nicaud, ; Liu, Ji, & Huang, ; Madzak, ; Zhu & Jackson, ). It presents several advantages as industrial host, including a vast repertoire of molecular tools and the ability to grow naturally in low cost substrates such as glycerol or molasses (Ledesma‐Amaro & Nicaud, ), or once engineered in xylose, raw starch, cellobiose, cellulose, or inulin (Guo et al, ; Ledesma‐Amaro, Dulermo, & Nicaud, ; Ledesma‐Amaro, Lazar et al, ; Wei et al, ; Zhao, Cui, Liu, Chi, & Madzak, ). Moreover, its metabolism, specifically the lipid metabolism, has been widely studied and characterized (Dulermo, Gamboa‐Melendez, Ledesma‐Amaro, Thevenieau, & Nicaud, ; Dulermo, Gamboa‐Melendez, Ledesma‐Amaro, Thevenieau, & Nicaud, ; Kerkhoven et al, ; Kerkhoven, Pomraning, Baker, & Nielsen, ; Qiao, Wasylenko, Zhou, Xu, & Stephanopoulos, ; Wasylenko, Ahn, & Stephanopoulos, ).…”

Section: Introductionmentioning

confidence: 99%

A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of β‐carotene

Larroude

Celińska

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et al. 2017

Biotech & Bioengineering

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The increasing market demands of β-carotene as colorant, antioxidant and vitamin precursor, requires novel biotechnological production platforms. Yarrowia lipolytica, is an industrial organism unable to naturally synthesize carotenoids but with the ability to produce high amounts of the precursor Acetyl-CoA. We first found that a lipid overproducer strain was capable of producing more β-carotene than a wild type after expressing the heterologous pathway. Thereafter, we developed a combinatorial synthetic biology approach base on Golden Gate DNA assembly to screen the optimum promoter-gene pairs for each transcriptional unit expressed. The best strain reached a production titer of 1.5 g/L and a maximum yield of 0.048 g/g of glucose in flask. β-carotene production was further increased in controlled conditions using a fed-batch fermentation. A total production of β-carotene of 6.5 g/L and 90 mg/g DCW with a concomitant production of 42.6 g/L of lipids was achieved. Such high titers suggest that engineered Y. lipolytica is a competitive producer organism of β-carotene.

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Section: Introductionmentioning

confidence: 99%

A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of β‐carotene

Larroude

Celińska

Back

et al. 2017

Biotech & Bioengineering

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275

237

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“…Despite an increased number of biotechnological applications performed by several wild or genetically engineered Y. lipolytica strains [13–15, 20–22] relatively few studies have focused on the metabolism, growth kinetics and product formation in mixed substrate fermentation [7, 23]. In general, dual substrate fermentation by oleaginous yeasts has been little investigated [24, 25]. Hen ce, the starting point of this work is to compare the growth of Y. lipolytica and products formation in dual substrate of glucose and glycerol versus mono-substrate fermentation.…”

Section: Introductionmentioning

confidence: 99%

Substrates and oxygen dependent citric acid production by Yarrowia lipolytica: insights through transcriptome and fluxome analyses

et al. 2017

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BackgroundUnlike the well-studied backer yeast where catabolite repression represents a burden for mixed substrate fermentation, Yarrowia lipolytica, an oleaginous yeast, is recognized for its potential to produce single cell oils and citric acid from different feedstocks. These versatilities of Y. lipolytica with regards to substrate utilization make it an attractive host for biorefinery application. However, to develop a commercial process for the production of citric acid by Y. lipolytica, it is necessary to better understand the primary metabolism and its regulation, especially for growth on mixed substrate.ResultsControlling the dissolved oxygen concentration (pO2) in Y. lipolytica cultures enhanced citric acid production significantly in cultures grown on glucose in mono- or dual substrate fermentations, whereas with glycerol as mono-substrate no significant effect of pO2 was found on citrate production. Growth on mixed substrate with glucose and glycerol revealed a relative preference of glycerol utilization by Y. lipolytica. Under optimized conditions with pO2 control, the citric acid titer on glucose in mono- or in dual substrate cultures was 55 and 50 g/L (with productivity of 0.6 g/L*h in both cultures), respectively, compared to a maximum of 18 g/L (0.2 g/L*h) with glycerol in monosubstrate culture. Additionally, in dual substrate fermentation, glycerol limitation was found to trigger citrate consumption despite the presence of enough glucose in pO2-limited culture. The metabolic behavior of this yeast on different substrates was investigated at transcriptomic and 13C-based fluxomics levels.ConclusionUpregulation of most of the genes of the pentose phosphate pathway was found in cultures with highest citrate production with glucose in mono- or in dual substrate fermentation with pO2 control. The activation of the glyoxylate cycle in the oxygen limited cultures and the imbalance caused by glycerol limitation might be the reason for the re-consumption of citrate in dual substrate fermentations. This study provides interesting targets for metabolic engineering of this industrial yeast.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-017-0690-0) contains supplementary material, which is available to authorized users.

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“…A study of 427 yeast strains from seawater, sediment, mud of salterns, guts of the marine fish and marine algae should also be mentioned here [47]. Industrial yeast Yarrowia lipolytica of marine origin is a biocatalyst of interest in metabolic engineering studies used to expand the substrate range [48]. Entries 9–12 in Table 1 are interesting primary articles along this line of research.…”

Section: Biorefinerymentioning

confidence: 99%

Enzymatic Processes in Marine Biotechnology

Trincone

2017

Marine Drugs

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In previous review articles the attention of the biocatalytically oriented scientific community towards the marine environment as a source of biocatalysts focused on the habitat-related properties of marine enzymes. Updates have already appeared in the literature, including marine examples of oxidoreductases, hydrolases, transferases, isomerases, ligases, and lyases ready for food and pharmaceutical applications. Here a new approach for searching the literature and presenting a more refined analysis is adopted with respect to previous surveys, centering the attention on the enzymatic process rather than on a single novel activity. Fields of applications are easily individuated: (i) the biorefinery value-chain, where the provision of biomass is one of the most important aspects, with aquaculture as the prominent sector; (ii) the food industry, where the interest in the marine domain is similarly developed to deal with the enzymatic procedures adopted in food manipulation; (iii) the selective and easy extraction/modification of structurally complex marine molecules, where enzymatic treatments are a recognized tool to improve efficiency and selectivity; and (iv) marine biomarkers and derived applications (bioremediation) in pollution monitoring are also included in that these studies could be of high significance for the appreciation of marine bioprocesses.

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Metabolic Engineering for Expanding the Substrate Range of Yarrowia lipolytica

Cited by 189 publications

References 88 publications

A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of β‐carotene

A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of β‐carotene

Substrates and oxygen dependent citric acid production by Yarrowia lipolytica: insights through transcriptome and fluxome analyses

Enzymatic Processes in Marine Biotechnology

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