Source: CHI BOTANIC INC. submitted to
VANILLA 2.0: A RELIABLE, SUSTAINABLE, DOMESTIC SUPPLY OF AUTHENTIC VANILLA PLANIFOLIA FLAVOR AND FRAGRANCE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1030057
Grant No.
2023-33523-39292
Cumulative Award Amt.
$175,000.00
Proposal No.
2023-01170
Multistate No.
(N/A)
Project Start Date
Jul 1, 2023
Project End Date
Feb 29, 2024
Grant Year
2023
Program Code
[8.2]- Plant Production and Protection-Biology
Project Director
Meuser, J. E.
Recipient Organization
CHI BOTANIC INC.
1962 MAIN ST STE 200 # 234
SARASOTA,FL 342369519
Performing Department
(N/A)
Non Technical Summary
Vanilla is a widely used ingredient found in thousands of products. Most commercial vanilla production has been offshored. The U.S. manufacturers that utilize natural vanilla must import this crop but this material often has issues with high prices, inconsistent supply chains, variation in quality, and imparts a heavy toll on local people and ecosystems where it is produced.We aim to solve the current issues with vanilla by the development of a commercial Vanilla planifolia plant cell culture. The liquid culture of plants is an established technology in which plants are grown as a fine suspension of small clumps or single cells. Unlike V. planifolia plants, an V. planifolia cell culture can be domestically-produced in a safe and high quality way without pesticides or adulterants.?Our high-throughput approaches will explore more V. planifolia genotype-phenotype and environment-phenotype space than ever before. This research will establish V. planifolia cell culture technology as an innovative and domestic way to produce vanilla.
Animal Health Component
80%
Research Effort Categories
Basic
20%
Applied
80%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
20122391030100%
Goals / Objectives
The overall objective of the proposal is to generate a vanilla cell culture for the use in fragrances, foods,drinks, or other products that contain vanilla. While the generation of plant cell cultures is guided bystandard tissue culture practices, the specific tissues, genotypes, hormone concentrations, and optimalmedium are plant species specific. Our Technical Objectives are to further expand the application of plantcell culture to cell suspension culture of vanilla and the production of valuable glycosides, specificallyvanillin. The specific objectives of the program can be enumerated as follows:1. Generate V. planifolia plant cell culture lines that contain a fluorescent reporter that correlates tothe expression of the phenylpropanoid biosynthetic pathway2. Identify environmental variables, elicitors, and chemicals that increase vanillin production.3. Isolate V. planifolia plant cell lines that have increased vanillin production.4. Quantitative determination of vanillin levels from best lines to confirm phenotype.
Project Methods
Technical Objective 1. Transformation of V. planifolia cultures.Task 1.1 Synthesis of Vanilla Planifolia Phenylpropanoid Pathway Reporter (pVaP3R) vectors.We propose to leverage the 5' upstream promoter regions of genes encoding three key enzymatic steps inthe biosynthesis of vanillin (Fig. 2) for the creation of transgenic fluorescent reporter plasmids.In order to generate the pVaP3R family of reporter plasmids, synthetic reporter fragments including: p35s::GFP::t35s (pVaP3R-1, + control), pPAL::GFP::t35s (pVaP3R-2), pVAN::GFP:t35s (pVaP3R-3) or pHBS::GFP::t35s (pVAP3R-4) will be cloned into the pCambria-1300-Pac1 multiple cloning site (MCS).Task 1.2 Transformation of V. planifolia cell suspension culturesWe propose to introduce the pVaP3R constructs outlined above (Fig. 2) into V. planifolia suspensioncultures using particle bombardment.Bombardment methods will be performed as described previously for maize(Vain et al, 1993). In brief, cultures will be grown to early log phase prior to gene introduction. Cellclumps and small cell clusters will be aseptically filtered through sterile glass fiber filters and placed onsemi solid media containing mannitol and sorbitol for 4 hours pre-bombardment to plasmolyze the targetcells. After bombardment, filters containing cells will be returned to media containing mannitol andsorbitol for recovery and then transferred to media without selective agent (hygromycin) for 4-7 days.After this additional recovery, bombarded cells will be transferred to hygromycin containing media forselection of transgenic cell lines.Task 1.3 Confirmation of positive controls and baseline GFP fluorescenceGFP expression in cell lines will be tracked and quantified using an automated image collection andanalysis system as described previously (Finer et al., 2006, Chiera et al., 2007). In brief, transgenic V.planifolia lines will be plated on various media in Petri dishes, and those dishes placed on the2-dimensional robotics platform for monitoring of GFP expression. Images will be collected from eachpiece of tissue, every hour for 100 hours for quantification of gfp expression and generation of time lapseanimations of tissue displaying gfp expression.Technical Objective 2. Identify Conditions and Elicitors that Increase VanillinTask 2.1 - Environmental and chemical elicitation of diverse phenotypes.Elicitors are chemicals that can trigger specific phenotypic responses in plants, oftenassociated with biotic or abiotic stresses. Some common eliciters include flagellin, LPS, salicylic acid,methyl salicylate, benzothiadiazole, benzoic acid, chitosan, and jasmonic acid. In addition, a chemicalgenomics approach will be taken to identify small molecules in the "Library of AcTive Compounds onArabidopsis" (LATCA) that stimulate vanillin production.Technical Objective 3. FACS to Isolate High Vanillin LinesTask 3.1 Fluorescence cell sorting for characteristic native fluorescence of Vanilla glycosides-filledphenylplast-type plastids.To select for Vanilla lines thatproduce increased levels of Vanilla glycosides, a mixed population of Vanilla cells will be analyzed andthe top 1% of cells with green fluorescences (GFP channel) will be sorted and isolated. This sortingprocedure will be repeated multiple times to enrich for cells that have increased green fluorescences andthus Vanilla glycosides. These cells will then be subjected to secondary screening with a fluorescent platereader and the subsequent top lines will have vanillin content measured via HPLC (Task 4).Task 3.2 Fluorescence cell sorting of pVaP3R Reporter LinesV. planifolia cell suspension cultures that have been transformed with pVaP3R constructs outlined in Task1 that produce GFP in response to upregulation of the phenylpropanoid pathway will be screened viaFACS.Task 3.3 Secondary screening via fluorescence plate reader.To assess vanillin content in lines isolated in Task 3.1, a Bio-tek Cytation 1 Cell Imaging Multi-ModeReader (Cyt1V) will be used to assay fluorescence from 96-well plate libraries.Technical Objective 4. Quantitation of Vanilla Glycosides (Vanillin) from Best LinesTask 4.1 Extraction and HPLC analysis of VanillinVanillin content of V. planifolia cell suspension cultures identified in Tasks 1-3 will be quantified. V.planifolia biomass will be isolated, hydrolyzed, and extracted. Extracts will be separated on an HPLCwith a C18 column using an isocratic mobile phase. Vanillin will be detected by measuring absorbance at271 nm (Adawiya 2020).Task 4.2 ConditioningIsolation of cells shown to accumulate VAN and correlated glucovanillin will be followed bysimulation of taditional vanilla bean curing process as well as treatment with commercial β-glucosidasesto liberate Vanilla glycosides like transformation of glucovanillin to vanillin.

Progress 07/01/23 to 02/29/24

Outputs
Target Audience:Chi Botanic was demonstrating the functional application of plant cell agriculture to multiple audience types throughout the project. First, the ability to transform the vanilla pod into a fast growing cell suspension is a real application of an abstract commercial possibility for financial investors looking to capitalize from this new form of agriculture. Representing this audience was a reporter from the weekly newletter of the venture capital firm AgFunder, who wrote an article detailing our USDA-funded vanilla project. The second target audience are those commercial sectors with applications of this new way to produce vanilla flavor and fragrance. The value that it could provide to their customer base goes beyond the organoleptic qualities of the vanillin molecule. We are developing an alternative to the vanilla plant that is more ethical, sustainable, and a potential domestic source beyond the Hawaiian islands. Perhaps most importantly, we target a far cheaper source for our audience of customers. Finally, we are also targeting the young scientists that are drawn to this new technology. Many have found the application to make vanilla very interesting because it is something of an exotic plant. It has been refreshing to watch students and young scientists gravitate towards learning in vitro methods and sterile techniques in order to be inspired to help transform a multicellular vanilla plant into a shaken, microbe-like cell suspension for the first time. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The Vanilla 2.0 project, in collaboration with the University of California, Riverside, has offered a graduate student (first generation, community college transfer) extensive training in advanced biotechnological techniques and scientific communication. This experience is complemented by participation in the UCR led NSF-funded Plants3D program, which merges plant biology with entrepreneurship, equipping participants with skills for innovation and commercialization. Through interdisciplinary training and professional networking, the program prepares future leaders to address agricultural and sustainability challenges. This grant has allowed for this student opportunities to grow as a scientist and entrepreneur focused in plant biology. How have the results been disseminated to communities of interest?A significant part of our project involved collecting Vanilla planifolia cultivars from several farms on the Big Island of Hawaii. During our visit, we engaged directly with vanilla farmers, discussing our objectives, methodologies, and potential impacts of our research on sustainable vanilla production. These interactions provided an opportunity to share knowledge, gather invaluable feedback, and foster partnerships grounded in mutual benefits and shared goals for the future of vanilla cultivation in Hawaii and with our new approach using plant cell culture. Additionally we were able to genotype the vanilla varieties that we obtained and let the farmers know what varieties they were growing, which was not known to them. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Our team visited several vanilla farms on the Big Island of Hawaii, where we collected various Vanilla planifolia cultivars. After securing high-quality genetic material for our research and development efforts from Hawaii we have successfully established three Vanilla planifolia cultivars in sterile in vitro culture systems (two from Hawaii and one other that was sourced from the University of Florida). These were used for callus production and are continuing to be propagated in sterile conditions for future use. Our research has led to the development of three distinct media types optimized for callus production in Vanilla planifolia. These media variations are designed to enhance cell division and growth, serving as a precursor to establishing cell lines for vanillin production. From these callus we established liquid suspension cultures. This achievement is a significant milestone towards commercial-scale vanillin production from plant cell culture. With our vanilla plant cell cultures we were able to establish a fluorescent activated cell sorting approach to isolate vanilla cells with high levels of vanillin by leveraging the fluorescent properties of vanillin itself. This method will be instrumental in selecting cell lines with enhanced vanillin biosynthesis capabilities. For a reverse genetic approach to increase vanillin production in our plant cell cultures, we designed and synthesized a transformation cassette for the overexpression of vanillin synthase. This genetic tool is designed to increase vanillin production in Vanilla planifolia cells by overexpressing a key enzyme in vanillin biosynthesis. To evaluate the function of the plasmid we successfully transformed Nicotiana tobacco cv. Little Dutch with the vanillin overexpression construct, which will be used to validate that the plasmid is functional in a model plant system. To optimize transformation in Vanilla planifolia we have identified the proper concentration of kanamycin for selecting transformed cells. This step is crucial for maintaining the integrity of our genetically engineered cell lines. Finally, our team has conducted Agrobacterium-based transformation experiments in Vanilla planifolia, resulting in putative transformation events that will be further evaluated for increased vanillin production.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Hann EC, Harland-Dunaway M, Garcia AJ, Meuser JE, Jinkerson RE. Alternative carbon sources for the production of plant cellular agriculture: a case study on acetate. Front Plant Sci. 2023 Oct 26;14:1104751. doi: 10.3389/fpls.2023.1104751. PMID: 37954996; PMCID: PMC10639172.