Developing filamentous fungal chassis for natural product production

The growing demand for green and sustainable production of high-value chemicals has driven the interest in microbial chassis. Recent advances in synthetic biology and metabolic engineering have reinforced filamentous fungi as promising chassis cells to produce bioactive natural products. Compared to the most used model organisms, Escherichia coli and Saccharomyces cerevisiae, most filamentous fungi are natural producers of secondary metabolites (SMs) and possess an inherent pre-mRNA splicing system and abundant biosynthetic precursors. In this review, we summarize recent advances in the application of filamentous fungi as chassis cells. Emphasis is placed on strategies for developing a filamentous fungal chassis, including the establishment of mature genetic manipulation and efficient genetic tools, the catalogue of regulatory elements, and the optimization of endogenous metabolism. Furthermore, we provide an outlook on the advanced techniques for further engineering and application of filamentous fungal chassis.