Improved Production of Lipids in Oleaginous Yeast

Synthetic Biology

Lipids have a many applications, such as in foods, cosmetics & fuels. Oleaginous yeasts can produce high amounts of lipids and can be engineered using synbio. Here, we propose the development of novel methods to produce lipids at increased capacity.

Project Team

Rodrigo Ledesma-Amaro
Rodrigo Ledesma-Amaro

Institutions

Imperial College London
Imperial College London
GB

Project Status

Clinical Stage
Not applicable
Patent Status
Patent not filed

Funding Opportunity

Opportunity type
Funding requested
$249,000
Funding allocated
$0

Background

Microbial lipids have many applications and contrary to their counterparts, animal fats, and vegetable oils, their production is more sustainable, does not compete with food industries, and can be scalable using less land and water. Yarrowia lipolytica, is a non-conventional organism that has been vastly studied in the last 15 years because of its lipid-producing capacity. The group of Dr Ledesma-Amaro, among others, has contributed to the development of synbio tools for this host, which has paved the way for an easier engineering process. One of the economic limitations in producing microbial lipids at scale is the downstream process - the extraction of the lipids. This is because microbial lipids are stored inside the cells. To extract them, the cells must be opened. This process requires energy, solvents and/or enzymes, which drastically increases production costs. In addition, with the lipids accumulating inside the cells, there is a limitation to how much lipids can be produced, which is constrained by the total number of cells and intracellular space available. To overcome these limitations and decrease the costs lipid production, they pioneered an approach that allowed the secretion of lipids in Yarrowia lipolytica to the culture broth, enabling easier extraction and purification (1). This POC study demonstrated the viability of the approach but leaves room for further improvement. In addition, the capacity to secrete lipids outside the cells, also opens the possibility to develop a continuous fermentation process not possible otherwise. This would allow better use of carbon resources since there’ll be no need to spend energy and resources on making new cells - an original set of cells can be immobilized in a bioreactor and used to continuously convert a low-cost substrate into valuable microbial lipids. (1) Combining metabolic engineering and process optimization to improve production and secretion of fatty acids. doi.org/10.1016/j.ymben.2016.06.004

Project Details

This project aims to create novel bioprocesses to produce microbial lipids. These processes will combine genetic and metabolic engineering with bioreactor and downstream optimization. To achieve these goals we will work in 2 main directions: 1. Creating non-Yarrowia oleaginous yeast strains with improved capacity to produce and secrete microbial lipids. 2. Exploring different bioprocess types to enable the production of microbial oils in a continuous manner. The project itself will be divided in different milestones, 1, 2 and 3 as specified below. For further details on the project specifics, please send us an inquiry.

Project Timeline

  • Strain engineering for efficient secretion

    Required Funding$83,000
    Statusplanned
    Duration8 Months

    We will develop novel strains and methods to secrete lipids and we will compare the production capacity of these strains with our best-secreted strain already constructed.

  • Continuous production of microbial lipids

    Required Funding$83,000
    Statusplanned
    Duration8 Months

    We will study different types of processes to maximize the production of lipids in a continuous manner using our previously developed strains able to secrete lipids. Both chemostat and turbidostat configurations will be tested. We will also explore different ways to immobilize cells in the bioreactor. Finally, we will also optimize the continuous recovery and extraction using different organic phases.

  • Optimization of microbial lipid production

    Required Funding$83,000
    Statusplanned
    Duration8 Months

    We will combine the best strains from milestone 1 with the best processes from milestone 2. The processes will be further optimized by exploring the use of different low-cost carbon sources, such as lignocellulosic materials or industrial waste streams.