Enzymatic synthesis of geranic acid and its protective effects against UVB-induced skin photodamage.
- 1PROYA Cosmetics Co., Ltd., Hangzhou, China.
Abstract
Background
Geranic acid (GA, E-3,7-dimethyl-2,6-octadienoic acid) is a natural monoterpenoid with antimicrobial,anti-inflammatory and antioxidant properties, holding great potential in cosmetics and pharmaceuticals. However, current chemical synthetic routes suffer from poor stereoselectivity and reliance on harsh reagents, restricting its scalable production. This study established a sustainable and stereoselective enzymatic route for producing high-purity GA from citral, and evaluated its protective effect against UVB-induced photodamage in keratinocytes.Methods
A novel geranial dehydrogenase (GeDH) from Pseudomonas sp. was heterologously expressed in Escherichia coli BL21 (DE3) via high-density fed-batch fermentation. GA was biosynthesized from citral using a GeDH/NADH oxidase (NOX) cofactor regeneration system, and characterized by GC-QTOF-MS and ¹H NMR spectroscopy. The anti-photodamage activity and underlying mechanisms of GA were systematically investigated in UVB-irradiated HaCaT keratinocytes.Results
The biocatalytic system achieved efficient citral-to-GA conversion with over 98% trans-stereoisomeric purity, and NOX-mediated cofactor recycling significantly improved process feasibility and economy. In UVB-exposed HaCaT cells, GA dose-dependently alleviated oxidative stress, restored mitochondrial homeostasis, and suppressed Ca²⁺ influx and pro-inflammatory cytokine secretion via downregulating the TRPV1/NF-κB axis. Furthermore, GA attenuated DNA damage, and inhibited the expression of senescence-associated proteins.Conclusion
This study provides a sustainable biomanufacturing strategy for high-purity GA. The biosynthesized GA exerts multi-layered photoprotection in keratinocytes, strongly supporting its development as a natural anti-photodamage active ingredient for cosmetic and dermatological applications.
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BibTeX
@article{lin2026enzymatic,
title = {{Enzymatic synthesis of geranic acid and its protective effects against UVB-induced skin photodamage.}},
author = {Jiaxin Lin and Ping Zhang and Xianzhe Wang and Lingling Xuan and Shuling Zhang and Jing Wang and Hu Huang},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1891436},
url = {https://europepmc.org/article/MED/42948097},
note = {CC BY},
}
RIS
TY - JOUR
TI - Enzymatic synthesis of geranic acid and its protective effects against UVB-induced skin photodamage.
AU - Jiaxin Lin
AU - Ping Zhang
AU - Xianzhe Wang
AU - Lingling Xuan
AU - Shuling Zhang
AU - Jing Wang
AU - Hu Huang
PY - 2026
DA - 2026/10/13
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1891436
UR - https://europepmc.org/article/MED/42948097
AB - Background Geranic acid (GA, E-3,7-dimethyl-2,6-octadienoic acid) is a natural monoterpenoid with antimicrobial,anti-inflammatory and antioxidant properties, holding great potential in cosmetics and pharmaceuticals. However, current chemical synthetic routes suffer from poor stereoselectivity and reliance on harsh reagents, restricting its scalable production. This study established a sustainable and stereoselective enzymatic route for producing high-purity GA from citral, and evaluated its protective effect against UVB-induced photodamage in keratinocytes.Methods A novel geranial dehydrogenase (GeDH) from Pseudomonas sp. was heterologously expressed in Escherichia coli BL21 (DE3) via high-density fed-batch fermentation. GA was biosynthesized from citral using a GeDH/NADH oxidase (NOX) cofactor regeneration system, and characterized by GC-QTOF-MS and ¹H NMR spectroscopy. The anti-photodamage activity and underlying mechanisms of GA were systematically investigated in UVB-irradiated HaCaT keratinocytes.Results The biocatalytic system achieved efficient citral-to-GA conversion with over 98% trans-stereoisomeric purity, and NOX-mediated cofactor recycling significantly improved process feasibility and economy. In UVB-exposed HaCaT cells, GA dose-dependently alleviated oxidative stress, restored mitochondrial homeostasis, and suppressed Ca²⁺ influx and pro-inflammatory cytokine secretion via downregulating the TRPV1/NF-κB axis. Furthermore, GA attenuated DNA damage, and inhibited the expression of senescence-associated proteins.Conclusion This study provides a sustainable biomanufacturing strategy for high-purity GA. The biosynthesized GA exerts multi-layered photoprotection in keratinocytes, strongly supporting its development as a natural anti-photodamage active ingredient for cosmetic and dermatological applications.
SN - 2296-4185
ER -