Recipient Organization
ARCH INNOTEK, LLC
4320 FOREST PARK AVE STE 303
SAINT LOUIS,MO 63108
Performing Department
(N/A)
Non Technical Summary
Carotenoids, the basic source of yellow, orange and red, are among the most common, naturally occurring pigments. Because of their antioxidant properties and colors, currently, carotenoids are used commercially as feed additives, natural food colorants,
dietary supplements and cosmetics and pharmaceutical industries. Currently, most of carotenoids used industrially are chemically synthesized from petrochemical sources, a disadvantage as chemical synthesis yields food safety issue as well as not environmentally friendly. Carotenoids produced from their natural source are projected to be the fastest-growing market segment owing to increasing consumers' preferences toward natural products. A major challenge for manufacturers is the high
production cost of natural products compared to the chemical synthetic versions, which limits the obtainable market. Without innovation, processes to isolate natural carotenoids cannot compete on price with the synthetic counterparts, particularly in aquaculture and poultry feed market. We aim to develop novel technologies which will allow us to reliably produce high-value carotenoids at low cost and sustainable commercial levels through yeast fermentation-based processes to satisfy the rapidly growing market demands of natural products for animal and human health. Our technology is based on bioengineering specialized General Regarded as Safe (GRAS) yeast which allows us the ability to make carotenoids more normally found elsewhere in nature. Our technologies have
multiple benefits, including a clean "natural" label, better product quality, improved supply chain, reduced production cost, and improved sustainability. Compared with the current petroleum-based synthetic method, our approach will meet its high yield and lower-cost and will surpass it with a clean, natural label. Our approach will exceed the low yield and high cost of natural source extraction. After commercial-scale production, we believe that our product would be widely used by the aquaculture and poultry industries and would replace current chemically synthesized product in the animal feed market. The aquaculture and poultry industries, and thus consumers, will benefit from our wholesome product.
Animal Health Component
30%
Research Effort Categories
Basic
50%
Applied
30%
Developmental
20%
Goals / Objectives
The major of the project is to develop a clean and sustainable source of carotenoids through low-cost fermentation using metabolically engineered (GRAS) yeast.
Since production of natural carotenoids from natural sources (plants or algae) is too expensive, most commercial carotenoids (e.g. astaxanthin) used in animal feed is synthetic and derived from petrochemical sources, which raises issues about food safety because the final product (salmon, trout, eggs, and chicken) will enter the human food supply chain. The major challenge for manufacturers is the high production cost from natural sources, which limits the obtainable market. Therefore, there is a strong desire and need in the aquaculture and poultry industries for a source of low-cost natural alternatives. The Phase I
research is to demonstrate the feasibility of using a novel yeast fermentation process to produce carotenoids with the same stereoisomeric configuration as the natural-sourced product.
Two objectives will be addressed in accomplishing the overall goal of the research.
Objective #1: To identify novel key enzyme(s) by whole-genome sequencing method. The putative genes will be examined by heterologous expression in yeast strain. Comparison with the HPLC and LC-MS profiles of the control strain will reveal the enzymes' functions.
Objective #2: To demonstrate the potential for a commercially-viable level of production. In order to demonstrate the potential for a commercially-viable level of production, the objective 2 will focus on increasing the supply of key precursor , acetyl-CoA, and
fermentation optimization. We propose two new approaches to increase cytoplasmic acetyl-CoA supply. In parallel to strain engineering, we will perform fermentation process development. We will use shake flasks to screen for optimal conditions. Key cultivation factors including pH and carbon/nitrogen (C/N) ratio, will be optimized. Also substrate co-feeding strategy will be used
to reduce metabolic burden for precursor synthesis. We will further validate these conditions ing bench-top bioreartor. After stepwise engineering and optimization of the fermentation process, we expect that over 1 g/L final product will be attainable after Phase I research.
Project Methods
The production of natural carotenoids from natural source is too expensive, most commercial carotenoids used in animal feed is synthetic and derived from petrochemical sources, which raises issues about food safety (potential toxicity and unknown by-products ). Although there are many disadvantages, the world market is still dominated by synthetic versions due to the lack of alternative sources. This Phase I project will apply synthetic biology and bioprocess optimization to develop a novel, safe, cost-
effective fermentation production process via metabolically-engineered GRAS yeast. Via whole genome sequencing and synthetic biology, novel key enzymes will be identified and integrated, along with supporting pathways, into yeast chromosomes. Product synthesis will be maximized via genetic modifications and fermentation optimization.