Every road leads to Rome: diverse biosynthetic regulation of plant cell wall-degrading enzymes in filamentous fungi <italic>Penicillium oxalicum</italic> and <italic>Trichoderma reesei</italic>.

Abstract Cellulases and xylanases are plant cell wall-degrading enzymes (CWDEs) that are critical to sustainable bioproduction based on renewable lignocellulosic biomass to reduce carbon dioxide emission. Currently, these enzymes are mainly produced from filamentous fungi, especially <italic>Trichoderma reesei</italic> and <italic>Penicillium oxalicum</italic>. However, an in-depth comparison of these two producers has not been performed. Although both <italic>P. oxalicum</italic> and <italic>T. reesei</italic> harbor CWDE systems, they exhibit distinct features regulating the production of these enzymes, mainly through different transcriptional regulatory networks. This review presents the strikingly different modes of genome-wide regulation of cellulase and xylanase biosynthesis in <italic>P. oxalicum</italic> and <italic>T. reesei</italic>, including sugar transporters, signal transduction cascades, transcription factors, chromatin remodeling, and three-dimensional organization of chromosomes. In addition, different molecular breeding approaches employed, based on the understanding of the regulatory networks, are summarized. This review highlights the existence of very different regulatory modes leading to the efficient regulation of CWDE production in filamentous fungi, akin to the adage that “every road leads to Rome.” An understanding of this divergence may help further improvements in fungal enzyme production through the metabolic engineering and synthetic biology of certain fungal species. [ABSTRACT FROM AUTHOR]