Week 1 HW: Principles and Practices

I am curious about exploring the potential of HTGAA utilising the Design Build Test and Learn strategy. I have recently done an Innovate UK project in which I used MoClo kits to design the synthesis of xanthone in yeast. I am curious about exploring the potential of the phenylpropanoid pathway and the plethora of useful chemicals that could be produced.

Hence, I am proposing this study “Engineered Naringenin production through Design Build Test and Learn Strategy”, as a committed listener, for which I would be interested to work in Victoria,Genspace or Designer Cells.I am currently based in UK and hence intereted in working on nodes in UK.

The study involving the metabolic engineering of Naringenin will be conducted under approved BSL-1 laboratory conditions, in accordance with institutional and biosafety guidelines. For in vitro cell cultures, commercially available human-derived cell lines will be used. No primary human subjects will be directly involved. All data collection, analysis and reporting will adhere to the principles of ethical research conduct.

Purpose

Naringenin (C15H12O5) is a novel bioactive compound within the flavonoid group, found naturally in the skin of citrus fruits. This citrus flavonoid is well known for its anti-inflammatory, antioxidant, and anticarcinogenic properties, and can support skin against the detrimental impacts of inflammaging. Outside skin care research, Naringenin has shown promising results in treating issues like obesity and cardiovascular diseases.

The primary source of Naringenin is citrus fruits, hence consuming a lot of natural resources and labour. What if we make the process economical and produce naringenin at lab scale? Sounds great and doable through synthetic biology.

Design

I propose engineering the phenylpropanoid pathway in S. cerevisiae to produce naringenin, utilizing the Design Build Test and Learn (DBTL) strategy of MoClo kits.

Work Packages

• WP1: Engineering the key enzymes in the phenylpropanoid to flavonoid pathway for naringenin biosynthesis
• WP2: Confirming the expression through proteomic and metabolomic analysis
• WP3: Formulation development for enhanced solubility and bioavailability
• WP4: Biological evaluation on skin models

Assumptions

The proposed study holds the potential to revolutionise the cosmetic industry by providing an economical source of Naringenin without relying on natural resources, hence a step towards preventing the depletion of natural resources.

Risks of Failure & Success

The study requires step-by-step, careful pathway optimisation through omics approaches to identify any bottlenecks in the engineering strategy in a heterologous host. If not followed accurately, the pathway will not lead to Naringenin production.

With attention to detail and proper record keeping, the project holds the potential to revolutionize the cosmetic industry.

References

• Cai, J., Wen, H., Zhou, H., Zhang, D., Lan, D., Liu, S., & Zhang, J. (2023). Naringenin: A flavanone with anti-inflammatory and anti-infective properties. Biomedicine & Pharmacotherapy, 164, 114990.
• Manchope, M. F., Casagrande, R., & Verri Jr, W. A. (2016). Naringenin: an analgesic and anti-inflammatory citrus flavanone. Oncotarget, 8(3), 3766.
• Österlund, C., Hrapovic, N., Lafon-Kolb, V., Amini, N., Smiljanic, S., & Visdal-Johnsen, L. (2023). Protective effects of naringenin against UVB irradiation and air pollution-induced skin aging and pigmentation. Cosmetics, 10(3), 88.
• Rashmi, R., Magesh, S. B., Ramkumar, K. M., Suryanarayanan, S., & SubbaRao, M. V. (2018). Antioxidant potential of naringenin helps to protect liver tissue from streptozotocin-induced damage. Reports of Biochemistry & Molecular Biology, 7(1), 76.

Biosecurity & Safety Considerations

I will propose constructive applications of the proposed research in the healthcare and beauty sectors, and not impede research and researchers. The governance action to be addressed should focus on the rights of the worker/researcher. As many projects are led by industry, researchers must not be treated as paid labour but are provided fair recognition, intellectual property rights, and equal participation in patent ownership.

I am extremely thankful to be a part of HTGAA-2026, looking forward to learning from world leading researchers in the field of synthetic biology.

Kind Regards,
Tehseen