Week 1 HW: Final Project Ideas
What you would like to biomanufacture and why ?
I’d like to make animal-free polydeoxyribonucleotide (PDRN) produced by microbial fermentation rather than extracted from salmon or trout milt.
PDRN was originally used in medicine to heal wounds, burns and diabetic ulcers. More recently, it has become a trendy skincare ingredient. The polymer is now known for its ability to promote skin regeneration and repair, and it is used as an injectable ‘skin booster’ in aesthetic dermatology.
The main problem with traditional PDRN is that it comes from salmonid gonads, which ties supply to fish harvests and to the availability and quality of aquaculture byproducts. This creates several issues: allergenic residual fish protein, incompatibility with vegan, halal and kosher requirements, and a supply ceiling if demand keeps growing. Although many skincare products on the market claim to contain PDRN, they actually contain phyto-PDRN, which is sourced from lab-grown wild ginseng or even roses. The main challenge with phyto-PDRN is that it does not match the molecular structure of salmon DNA fragments. I would like to bridge the gap between true clinical efficacy and full vegan compliance through precision fermentation. I am also personally a big fan of skincare, and I hope everyone can have the opportunity to use these products without worrying about allergens or animal-derived ingredients.
What living system would you use ?
I would use E. coli, because it is one of the most widely used bacteria in industry and research. Many companies already use it to produce large quantities of DNA for vaccines and therapies, as well as alternative proteins, so there is a large body of work I can draw on.
I would first design a plasmid carrying a chosen DNA sequence and transform it into E. coli cells. The bacteria would be cultured in a fermenter with glucose as the carbon source, along with other nutrients such as ammonium salts, phosphates, magnesium and trace metals. The fermentation would run aerobically at 37 °C under controlled pH, with glucose fed at a controlled rate to avoid the accumulation of acetic acid. The fermentation would be stopped once a target biomass was reached, measured by OD600 or dry cell weight (DCW). The broth would then be harvested by centrifugation and the cells lysed. Purification would follow: first the removal of larger unwanted molecules, then anion exchange and hydrophobic interaction chromatography to isolate the plasmid DNA and wash away cellular impurities. Finally, nuclease digestion and tangential flow filtration (TFF) would yield a purified solution of short DNA fragments suitable for use as PDRN. The specific approach to nuclease digestion is still being worked out, since the reaction is relatively difficult to control. The process assumes that the bacteria can replicate the designed plasmid faithfully and that byproducts can be removed to achieve high purity.
How would you use automation ?
Before establishing a protocol, there would be many variables to test such as strain, temperature, feed rate, harvest time and growth time in order to find the conditions that work best. I would use design of experiments (DoE) to set up a range of experimental conditions in 96-well plates. When running the experiments, I would use a liquid handler to collect time-point samples, especially when more than 100 samples need to be taken. Doing that by hand with a pipette would take a very long time and would introduce errors. A liquid handler would also ensure that sampling is consistent.
How much would you need to make, and how long would it take?
This calculation is based on aesthetic use in skincare. Using the Medicube PDRN Pink Peptide Serum as a baseline, each unit contains 300 mg of PDRN, or 1% (10,000 ppm) of the formulation. 1According to Medicube’s official website, there are 29 products in their PDRN line.2 APR Corp, Medicube’s parent company, reports that 50 million units of the PDRN line have been sold.3
PDRN per unit: 300 mg Units per year: 50 million ÷ 29 ≈ 1.7 million
Total PDRN needed per year: 1.7 million × 300 mg ≈ 517 kg
Assuming an overall downstream yield of 70%:
517 kg ÷ 0.7 ≈ 739 kg/year rounded to a target of 750 kg/year.
Assuming a crude fermentation titre of 1 g/L 4 and 50% product recovery:
Culture volume required: 750,000 g ÷ 0.5 g/L = 1,500,000 L/year
Batches at 2,000 L working volume: 1,500,000 L ÷ 2,000 L = 750 batches/year
What don’t you know yet?
Much of this is based on assumptions. From my experience working with other bacteria, purifying a target product is extremely difficult, and the actual process parameters remain a significant unknown. The typical doubling time for E. coli is 30 minutes in rich medium 5, but without knowing the final process conditions I cannot yet estimate how long each batch would take. A great deal of small-scale experimentation would be needed to confirm that the process works before scaling up.
Another unknown is whether the DNA can be cut to the right size consistently during nuclease digestion, since this is a relatively complex process. Because PDRN is applied to the human body, I also do not know whether bacterially produced DNA would perform in the same way as salmon-derived PDRN — whether it would actually help to rejuvenate skin, or have no effect at all.
References
- Anthropic. (2026). Claude (Opus 5)
- Chae, D., Oh, S.-W., Choi, Y.-S., Kang, D.-J., Park, C.-W., Lee, J., & Seo, W.-S. (2025). First report on microbial-derived polydeoxyribonucleotide: A sustainable and enhanced alternative to salmon-based polydeoxyribonucleotide. Current Issues in Molecular Biology, 47(1), 41. https://doi.org/10.3390/cimb47010041
Appendix (AI prompts)
- Suggest ideas for products I could biomanufacture, across medicine, materials, food, energy, art, design, or architecture.
- What about PDRN?
- Is all PDRN in cosmetics derived from animals?
- Are there skincare materials still made from animals or plants rather than microbes?
- What are the limitations of this paper on microbial PDRN?