Data from: A synthetic biology and green bioprocess approach to recreate agarwood sesquiterpenoid mixtures

Certain endangered Thymelaeaceous trees are major sources of the fragrant and highly valued resinous agarwood, comprised of hundreds of oxygenated sesquiterpenoids (STPs). Despite growing pressure on natural agarwood sources, the chemical complexity of STPs severely limits synthetic production. Here, we catalogued the chemical diversity in 58 agarwood samples by two-dimensional gas chromatography–mass spectrometry and partially recreated complex STP mixtures through synthetic biology. We improved STP yields in the unicellular alga Chlamydomonas reinhardtii by combinatorial engineering to biosynthesise nine macrocyclic STP backbones found in agarwood. A bioprocess following green-chemistry principles was developed that exploits ‘milking’ of STPs without cell lysis, solvent–solvent STP extraction, solvent–STP nanofiltration, and bulk STP oxy-functionalisation to obtain terpene mixtures like those of agarwood. This process occurs with total solvent recycling and enables continuous production. Our synthetic-biology approach offers a sustainable alternative to harvesting agarwood trees to obtain mixtures of complex, fragrant, oxygenated STPs.

部分濒危瑞香科（Thymelaeaceous）树种是香气馥郁、经济价值极高的树脂类沉香（agarwood）的主要来源，该类沉香含有数百种含氧倍半萜（oxygenated sesquiterpenoids, STPs）。尽管天然沉香资源所受的开发压力与日俱增，但含氧倍半萜的化学复杂性严重限制了其人工合成生产。本研究通过二维气相色谱-质谱联用技术（two-dimensional gas chromatography–mass spectrometry）对58份沉香样本的化学多样性进行了系统表征，并借助合成生物学手段部分复刻了复杂的含氧倍半萜混合组分。本研究通过组合工程技术改造单细胞藻类莱茵衣藻（Chlamydomonas reinhardtii），提升了其含氧倍半萜的合成产量，成功生物合成了沉香中存在的9种大环含氧倍半萜骨架（macrocyclic STP backbones）。本研究开发了一套遵循绿色化学原则（green-chemistry principles）的生物制备工艺，该工艺整合了无需细胞裂解（cell lysis）的含氧倍半萜在线采收、溶剂-溶剂萃取、溶剂-含氧倍半萜纳滤以及大规模含氧倍半萜含氧官能化修饰步骤，可获得与天然沉香组分相似的萜类混合产物。该工艺可实现溶剂完全循环利用，并支持连续化生产。本研究的合成生物学策略为通过采伐沉香树获取复杂香气型含氧倍半萜混合产物提供了可持续替代方案。