Center Partnership Funding: Modeling metabolic pathways of local Cyanobacteria and Bacilli strains

​​Objectives of the collaboration with Chalmers University of Technology

The following are the two main strategic objectives:

1. Developing the capacity of local Cyanobacteria for production of biomass and biofuels

In order to reduce the costs and time required for development of MCFs, it is necessary to develop novel technologies, and in particular enable better integration of novel biological findings into a quantitative modeling framework. The Archer Lab has created a library of 48 Red Sea cyanobacteria (group 1, 2 and 3) that have been prescreened for rapid biomass accumulation. Genome scaffolds have been generated for 24 of these strains that show potential as producers of biomass or have advantageous properties of lipid metabolism, which can be geared towards the production of biofuels. Our objective is to develop metabolic optimization strategies to guide the engineering of Cyanobacteria for increased growth rate and biomass production. The approach will be based on advanced genome-scale metabolic models (GEMs), enhanced by integration of different layers of "omics" data. We plan to focus on up to 10 most promising strains and use GEMs and other tools for in silico optimization of biomass production and the lipid metabolism and experimentally verify the results at the CBRC laboratories. In addition to model-driven interventions, we will also use adaptive laboratory evolution (ALE) to speed up biomass accumulation in different growth regimes, subject to feasibility. The preliminary data from metagenomics libraries generated at CBRC indicate a large variety of lipases in cyanobacterial genomes. These industrially relevant enzymes could represent a tremendous potential for commercial applications. To unlock this potential, we will perform a large-scale purification and characterization of over 100 different lipases. This work will be done at the protein expression and characterization platform at Chalmers. Delivery of the local strains and pure raw sequencing data of cyanobacterial genomes will be provided by the Archer's Lab. 

2. Developing local Bacilli into cell factories capable of using sea water

We have developed a pipeline for analyzing the secondary metabolism of Bacilli using over 100 genomes that are available in public repositories. This will be used to explore the capacity of the local Bacillus species, isolated from the Red Sea environmental samples. CBRC has a collection of over 50 local Bacillus strains  awaiting sequencing of their genomes for which GEMs will be constructed and classified according to their capacity to synthesize interesting secondary metabolites, siderophores and antimicrobials. Next, we will explore their transformability and capacity for growth on media based on saline water. Finally, we will focus on 10 most promising strains, and develop a tool-kit for genome editing. The Mijakovic laboratory at Chalmers (Prof Ivan Mijakovic is part of Prof Nielsen's team) has extensive experience in optimizing transformability of various strains of Bacilli, implementing advanced tools for seamless genetic engineering (knockouts, knock-downs, promoter tuning, heterologous gene expression) and CRISPR/Cas9 technology for simultaneous large-scale genome editing. The final objective will be to have a pilot strain, derived from a local Bacillus species, amenable for genetic engineering and optimized for growth in the bioreactor, on a medium based on salt water. Since desalination of seawater is a very energy-intensive process, we aim to develop white biotechnology by providing a bacterial workhorse that can tolerate high salinity, and thus reduce the cost of production by bypassing desalination. The fully annotated genomes of the local strains of Bacilli will be provided by the Bajic team.  

Participants

  • All CBRC PIs
  • Jens Nielsen, Chalmers University of Techonlogy
  • Ivan Mijakovic, Chalmets UNiversity of Technology

 

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