Core Viewpoint - The article discusses the sustainable and large-scale production of sandalwood essential oil through synthetic biology, addressing the resource scarcity and high costs associated with natural sandalwood [1][3]. Group 1: Sandalwood Essential Oil Overview - Sandalwood essential oil, derived from sandalwood heartwood, is highly valued for its unique woody fragrance and is used in perfumes, cosmetics, pharmaceuticals, and religious ceremonies [1]. - The slow growth of sandalwood trees, which take decades to mature, along with overharvesting, has led to a significant increase in market prices, approximately $2,500 per kilogram, and unstable supply [1]. Group 2: Synthetic Biology Approach - The research team at the Tianjin Institute of Industrial Biotechnology has successfully developed a yeast cell factory capable of producing sandalwood alcohol, achieving a record yield of 10.4 g/L, which is the highest reported in literature [3][4]. - The team utilized subcellular compartment engineering to enhance the production process, specifically targeting the peroxisome for enzyme localization, which significantly improved the conversion rates of sandalwood precursors [4]. Group 3: Research and Development Achievements - The study demonstrated a 5.1-fold increase in total yield of sandalwood alcohol and sandalwood olefin, reaching 0.9 g/L, with further innovations leading to a conversion rate increase to 60.6% [4]. - The research has received funding from various national programs and has resulted in multiple patent applications, with findings published in the Journal of Agricultural and Food Chemistry [5].

Core Insights - The article discusses the innovative use of synthetic biology to produce sandalwood essential oil sustainably, addressing the scarcity and high cost of natural sandalwood resources [2][3][15] Group 1: Research Breakthroughs - The research team developed a P450 enzyme peroxisome surface display technology, overcoming catalytic bottlenecks and achieving a record production yield of 10.4 g/L of sandalwood alcohol [3][5] - Initial attempts to synthesize sandalwood alcohol resulted in low yields, prompting the team to optimize the supply of acetyl-CoA and reducing power by targeting key enzymes to peroxisomes [5][10] - The innovative strategy of displaying P450 enzymes on the peroxisome surface significantly improved the proximity of the enzyme to the substrate, increasing sandalwood alcohol yield to 1.3 g/L and conversion rate to 36.2% [7][10] Group 2: Production Optimization - The team induced the proliferation of peroxisomes in engineered yeast, which increased the number of "factories" for storing acetyl-CoA and expanded the membrane surface area for enzyme anchoring, leading to a 42.6% increase in sandalwood alcohol yield and a conversion rate of 60.6% [10][12] - The optimized strain was scaled up in a 5L fermentation tank, achieving a record yield of 13.1 g/L of sandalwood olefin and 10.4 g/L of sandalwood alcohol, with a conversion rate of 44.2% [12][14] - The cost of producing sandalwood essential oil using this method is projected to be under $100 per kilogram, significantly lower than the market price of $2500 per kilogram [12][15] Group 3: Implications and Future Prospects - The research demonstrates the potential of peroxisome engineering in synthesizing high-value natural products, particularly those involving complex terpenes catalyzed by P450 enzymes [14][15] - The significant reduction in production costs for sandalwood essential oil could transform the traditional supply chain reliant on scarce plant resources, contributing to the conservation of endangered sandalwood species [15]