Source: DAST LLC dba Cyanosun Energy submitted to NRP
ENGINEERING PHOTOSYNTHETIC CYANOBACTERIA TO PRODUCE THE ENERGY-DENSE FUEL FARNESENE FROM CARBON DIOXIDE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0228949
Grant No.
2012-33610-19541
Cumulative Award Amt.
$99,875.00
Proposal No.
2012-00437
Multistate No.
(N/A)
Project Start Date
Jun 15, 2012
Project End Date
Feb 14, 2013
Grant Year
2012
Program Code
[8.8]- Biofuels and Biobased Products
Recipient Organization
DAST LLC dba Cyanosun Energy
1006 32nd Ave
Brookings,SD 57006
Performing Department
(N/A)
Non Technical Summary
The goal of the project is to genetically engineer photosynthetic cyanobacteria that will synthesize farnesene from carbon dioxide. The work will then involve shutting down pathways that compete for carbon in an attempt to maximize the amount of farnesene that can be produced. Then we will do tolerance testing by culturing the cyanobacteria in varying concentrations of the end product(s) in order to determine the optimal culturing conditions. This work will develop an engineered cyanobacterium capable of converting CO2 into farnesene (C15H24), a long-chain hydrocarbon with an energy density of 47 MJ/Kg, heat of vaporization of 0.24 MJ/Kg, and octane of 89.7. The cells would excrete farnesene into the recirculating culture fluid, where it would be recovered by low-cost phase separation for use as an energy-dense, infrastructure compatible biofuel. We have already established the validity of this "cyanofactory" platform by engineering Anabaena to produce the ten-carbon alcohol linalool. Farnesene has a much higher energy density and thus would be a more desirable 3rd generation biofuel.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
51124202000100%
Goals / Objectives
In Phase I, we will evaluate the feasibility of producing farnesene from an engineered cyanobacterium to achieve a titer of about 1 g/L. Low-cost phase separation will be used for direct recovery of farnesene, so that cells and culture fluid can be recycled. We anticipate that we will be able to achieve this level of farnesene production through a combination of approaches: Our Phase I objectives will include: 1) screening two cyanobacteria strains and three farnesene synthase (FaS) genes for farnesene production using a shuttle vector approach, 2) inserting the best FaS gene into the chromosome of the best cyanobacterium for stable expression, and 3) increasing carbon flow to farnesene by shutting off glycogen production.
Project Methods
Objective 1: Identify the best combination of cyanobacterial strains and farnesene synthase (FaS) genes for farnesene production by using the shuttle vector approach To quickly screen for the best combination of cyanobacterial strain and farnesene synthase (FaS) gene, we will use the shuttle vector method as it is both more efficient and faster than chromosomal integration. Since psbA promoter is highly conserved in cyanobacteria, we should be able to use these three constructs to screen the two cyanobacterial strains to identify the best farnesene-producing combination. The constructs will be individually introduced into the two cyanobacterial strains by conjugation. Transformants will be selected and grown to assess farnesene production. Objective 2: Integrate the best farnesene synthesis gene into the chromosome of the best cyanobacteria strain for stable expression. Using a shuttle vector will allow us to quickly screen for the best FaS gene - cyanobacteria combination, but the drawback is that an antibiotic selection pressure (extra cost) is needed to retain the plasmid in the cell during propagation. Once the ideal combination is identified, a stable farnesene-producing cyanobacterial strain will be created by the chromosomal integration approach. Objective 3: Block glycogen production to increase fixed carbon flow to farnesene, thus establishing the feasibility of using metabolic flux corrections to increase yield and productivity. To redirect carbon flow to the MEP pathway for farnesene production, we will block glycogen synthesis by inactivating glucose-1-phosphate adenylyltransferase, which catalyzes the first committed step in glycogen biosynthesis. Only one glucose-1-phosphate adenylyltransferase gene is found in the genome of cyanobacteria, thus we can block glycogen synthesis by inactivating the all4645 gene using double crossover knockout approach.Carbon flux-altered transgenic cultures will be evaluated for farnesene yield and productivity as described previously. Achieving this objective will demonstrate the feasibility of using additional metabolic flux corrections to further increase carbon flow to farnesene, hence boosting yield and productivity.

Progress 06/15/12 to 02/14/13

Outputs
Target Audience: Producing farnesene from CO2 will reduce U.S. dependence on foreign oil and help achieve energy independence, while reducing greenhouse gas emissions of biorefineries and coal power plants. In addition to fuel use, farnesene is a valuable industrial chemical that could be used to generate chemicals currently derived from petroleum. This cyanofactory process would be deployed at biofuel and coal fired power plants, as they are abundant sources for unutilized CO2, as well as low grade heat and water emissions (additional waste streams). Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Two different FaS genes (AFS1 and PaTPS-Far) were obtained that were expressed in two different cyanobacteria species, Anabaena 7120 and Nostoc punctiforme. These species were selected due to their ability to fix nitrogen and their robustness during farnesene tolerance testing. Of the two farnesene synthases, only PaTPS-Far was expressed in the cyanobacterium. Although protein expression was confirmed in each cyanobacteria, GC-MS analysis failed to detect farnesene being produced from the cultures. To address this problem, we codon-optimized the PaTPS-far gene in the shuttle plasmid to create pZR1406, and transferred it into both Anabaena 7120 and N. punctiforme for protein expression. Of the two cyanobacteria strains, only Anabaena 7120 produced farnesene, which was verified through GC-MS. We then conducted a 15-day farnesene production trial by growing the Anabaena 7120 strain harboring pZR1406 and capturing the volatized farnesene using a 2SV capture column. We measured a maximum farnesene production rate of 1.30±1.3 µg farnesene·L-1·hr-1 from days 13 through 15, and an overall volumetric productivity of 0.85±0.03 µg·L-1·hr-1. However, as cell mass increased we observed a dramatic decrease in specific farnesene productivity, which we attribute to light shading since high cell densities limit the number of photons harvested by each cell. A 2-gene operon was successfully integrated into the Anabaena 7120 chromosome, consisting of an FBP/SBP gene to increase carbon fixation and the optimized PaTPS-far gene, which was shown to enable Anabaena 7120 to produce farnesene. This gene was inserted into the middle of all4645 to block glycogen synthesis and allow more carbon into the MEP pathway to produce farnesene. Currently, we have been unable to detect farnesene in this culture, which we attribute to either: 1) a mutation in the inserted FBP/SBP-FaS operon or 2) low FaS protein levels in the cyanobacteria, due to a single gene copy of the optimized PaTPS-far gene in the chromosome. Further protein analysis and gene sequencing will be performed to resolve this problem.

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