Synthetic Biology Expands the Industrial Potential of Yarrowia lipolytica

Markham, Kelly A.; Alper, Hal S.

doi:10.1016/j.tibtech.2018.05.004

Cited by 111 publications

(67 citation statements)

References 72 publications

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“…For these reasons, Y. lipolytica, a GRAS strain, has attracted great attention in recent years, especially for the production of terpenoids. Several useful synthetic biology tools have been aiding the creation of new and better performing Y. lipolytica strains [42,43]. To date, the highest yields of lipid, lycopene and carotene produced via microbial cell factories have been achieved by using engineered Y. lipolytica strains [7,12].…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Yarrowia lipolytica , an unconventional and oleaginous yeast, has attracted an increasing attention in recent years (Darvishi, Ariana, Marella, & Borodina, ; Hussain et al, ; Markham and Alper, ; Xie, ) and has been exploited to produce a variety of products, such as fatty acid derivatives (Tai & Stephanopoulos, ; Xue et al, ), succinic acid (Cui et al, ; C. Gao et al, ), erythritol (Carly et al, ; Mirończuk, Biegalska, & Dobrowolski, ), and lipids (Qiao, Wasylenko, Zhou, Xu, & Stephanopoulos, ). Y. lipolytica is also an excellent host for the production of secondary metabolites such as α‐farnesene (Yang, Nambou, Wei, & Hua, ), lycopene (Matthäus, Ketelhot, Gatter, & Barth, ), and β‐carotene (S. Gao et al, ; Larroude et al, ), because it contains many precursors and cofactors.…”

Section: Introductionmentioning

confidence: 99%

Homology‐independent genome integration enables rapid library construction for enzyme expression and pathway optimization in Yarrowia lipolytica

Cui

Xin

Zheng

et al. 2018

Biotech & Bioengineering

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Yarrowia lipolytica is an important oleaginous industrial microorganism used to produce biofuels and other value-added compounds. Although several genetic engineering tools have been developed for Y. lipolytica, there is no efficient method for genomic integration of large DNA fragments. In addition, methods for constructing multigene expression libraries for biosynthetic pathway optimization are still lacking in Y. lipolytica. In this study, we demonstrate that multiple and large DNA fragments can be randomly and efficiently integrated into the genome of Y.lipolytica in a homology-independent manner. This homology-independent integration generates variation in the chromosomal locations of the inserted fragments and in gene copy numbers, resulting in the expression differences in the integrated genes or pathways. Because of these variations, gene expression libraries can be easily created through one-step integration. As a proof of concept, a LIP2 (producing lipase) expression library and a library of multiple genes in the β-carotene biosynthetic pathway were constructed, and high-production strains were obtained through library screening. Our work demonstrates the potential of homology-independent genome integration for library construction, especially for multivariate modular libraries for metabolic pathways in Y. lipolytica, and will facilitate pathway optimization in metabolic engineering applications.

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“…This approach would make it possible to efficiently complete many tasks and to acquire a specific product profile compartmentalizing molecular components of each pathway, transcriptional regulators, and chemical intermediates in each different microbial individual. Nevertheless, the use of this technology would face many drawbacks until it is approved to be used in fermented foods, in spite of being the focus of several studies in other similar fields [94][95][96].…”

Section: Trends and Perspectivesmentioning

confidence: 99%

Pursuing the Perfect Performer of Fermented Beverages: GMMs vs. Microbial Consortium

Aldrete-Tapia¹,

Miranda-Castilleja²,

Arvizu-Medrano³

et al. 2019

Frontiers and New Trends in the Science of Fermented Food and Beverages

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Fermented beverages are widely diverse around the world and their quality is largely based on the organoleptic characteristics developed by the metabolism of the microorganisms present during fermentation. In order to achieve controllable processes in fermented beverages along with organoleptic complexity, two divergent approaches have been followed in terms of inoculum development: (1) the inoculation of multiple microorganisms, intending to promote synergism and favor organoleptic complexity derived from the metabolic diversity, and (2) the genetic modification of a single strain with the intention that it performs multiple functions. In this chapter, we discuss these divergent approaches, their achievements and perspectives.

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Synthetic Biology Expands the Industrial Potential of Yarrowia lipolytica

Cited by 111 publications

References 72 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

Homology‐independent genome integration enables rapid library construction for enzyme expression and pathway optimization in Yarrowia lipolytica

Pursuing the Perfect Performer of Fermented Beverages: GMMs vs. Microbial Consortium

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