Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose. First, we engineer E. coli to produce between 300 and 700 mg/L of six different halogenated tryptophan precursors. Second, we harness the native promiscuity of multiple downstream enzymes to access unexplored regions of metabolism. Finally, through modular co-culture fermentations, we demonstrate a plug-and-play bioproduction platform, culminating in the generation of 26 distinct halogenated molecules produced de novo including precursors to prodrugs 4-chloro- and 4-bromo-kynurenine and new-to-nature halogenated beta carbolines.

含卤素分子在现代社会中无处不在，并呈现出独特的化学可能性。总体而言，这些分子的从头发酵和合成途径构建仍然相对未得到充分探索，并且可以在纺织、农用化学品和制药等行业中解锁具有令人兴奋的新应用的分子。在这里，我们报告了一个混合搭配共培养平台，可以在大肠杆菌中从葡萄糖中重新产生大量卤化色氨酸衍生物。首先，我们对大肠杆菌进行了改造，使其能够生产 300 至 700 mg/L 的六种不同的卤化色氨酸前体。其次，我们利用多种下游酶的天然混杂性来进入未探索的代谢区域。最后，通过模块化共培养发酵，我们展示了一个即插即用的生物生产平台，最终产生了 26 种从头生产的不同卤化分子，包括前药 4-氯-和 4-溴-犬尿氨酸的前体以及新的药物前体。 -天然卤代β咔啉。