Plant-sourced aromatic amino acid (AAA) derivatives are a vast group of compounds with broad applications. Here, we present the development of a yeast consortium for efficient production of (S)-norcoclaurine, the key precursor for benzylisoquinoline alkaloid biosynthesis. A xylose transporter enables the concurrent mixed-sugar utilization in Scheffersomyces stipitis, which plays a crucial role in enhancing the flux entering the highly regulated shikimate pathway located upstream of AAA biosynthesis. Two quinate permeases isolated from Aspergillus niger facilitates shikimate translocation to the co-cultured Saccharomyces cerevisiae that converts shikimate to (S)-norcoclaurine, resulting in the maximal titer (11.5 mg/L), nearly 110-fold higher than the titer reported for an S. cerevisiae monoculture. Our findings magnify the potential of microbial consortium platforms for the economical de novo synthesis of complex compounds, where pathway modularization and compartmentalization in distinct specialty strains enable effective fine-tuning of long biosynthetic pathways and diminish intermediate buildup, thereby leading to increases in production.

植物来源的芳香氨基酸 (AAA) 衍生物是一大类具有广泛应用的化合物。在这里，我们展示了用于高效生产 ( S )-去甲乌碱的酵母菌群的开发，(S)-去甲乌碱是苄基异喹啉生物碱生物合成的关键前体。木糖转运蛋白能够在树干树干酵母中同时利用混合糖，这在增强进入位于 AAA 生物合成上游的高度调控的莽草酸途径的通量方面发挥着至关重要的作用。从黑曲霉中分离出的两种奎宁酸通透酶促进莽草酸易位至共培养的酿酒酵母，将莽草酸转化为 ( S )-去甲乌酸，产生最大滴度 (11.5 mg/L)，比报道的滴度高近 110 倍。酿酒酵母单一栽培。我们的研究结果放大了微生物联盟平台在复杂化合物的经济从头合成方面的潜力，其中不同特种菌株中的途径模块化和区室化能够有效地微调长生物合成途径并减少中间积累，从而导致产量增加。