Current Progress of Natural Product Export by Yeast

Bioactive natural products are promising for diverse applications, prompting their efficient synthesis in microbial cell factories, enabled by advances in synthetic biology. However, the metabolic burden caused by the intracellular accumulation of natural products impairs cell growth and limits final production. Therefore, relieving the metabolic burden of microbial cell factories has emerged as an attractive strategy to enhance the production of natural products. Here, we focus on the recent advances in the yeast species Saccharomyces cerevisiae, Yarrowia lipolytica, and Rhodosporidium toruloides for enhancing the synthesis of natural products (with a focus on terpenes) by relieving the metabolic burden from intracellular accumulation. Three strategies to lower this metabolic burden are reviewed: 1. overexpressing and engineering transporters, 2. changing membrane structure, and 3. In situ extraction. Future directions in natural product export are summarized and may help reify efficient, sustainable, and economically viable natural product synthesis.