Filamentous fungi are widely distributed in nature, capable of producing organic acids, enzymes, and a variety of natural products such as polyketides, alkaloids, and terpenoids that hold significant value for human life (Keller et al., 2005; Liu et al., 2023; Strong et al., 2022; Yuan et al., 2022). In addition, certain species, owing to their exceptional protein secretion capacity, sophisticated post-translational modification machinery, and food-grade safety, have emerged as important “cell factories” in biotechnology and industrial fermentation (Strong et al., 2022). They are widely employed across the food, pharmaceutical, and feed industries (Fig. 1) (Li et al., 2020; Li et al., 2022b, Li et al., 2022a; Ntana et al., 2020).

During submerged fermentation, the morphological architecture of filamentous fungi is regarded as one of the key industrial challenges in the biotechnology sector (El Enshasy, 2022). These organisms exhibit a wide diversity of morphologies, with different hyphal forms being more suited to the production of specific products (Meyer et al., 2021). For instance, the expression of protein-based products tends to favor highly-branched dispersed mycelia to facilitate secretion at the tips (Fitz et al., 2019), while organic acids prefer highly-branched pellets to match the metabolic phase (Yin et al., 2017). Moreover, the growth mode and morphological characteristics of hyphae directly influence fermentation performance, including production rate, product quality, and adaptability under varying cultivation conditions (Lu et al., 2024). Consequently, understanding and controlling hyphal morphology is of critical importance for fermentation process optimization and the achievement of efficient industrial production.

With the growing recognition of the importance of filamentous fungal morphology in industrial production, a variety of strategies have been developed to enhance the expression levels of target products (Cairns et al., 2019b; Krull et al., 2013; Meyer et al., 2021). These include controlling cultivation conditions, adding microparticles to the growth medium, and regulating the expression of morphological genes and associated signaling pathways (Table 1). Although significant progress has been made in morphological regulation of filamentous fungi, challenges remain in its large-scale industrial application (Jo et al., 2023). One major hurdle lies in the considerable differences in morphogenetic mechanisms among fungal species, which limit the universality of current regulation strategies (Riquelme et al., 2018). Furthermore, due to the difficulty in handling filamentous fungi and the lack of efficient screening and verification tools, the biological mechanisms of morphological regulation have not been fully elucidated, and stable and rational regulation of hyphal morphology has not yet been achieved (Krull et al., 2013).

Based on the necessity of regulating filamentous fungal morphology, several reviews have systematically summarized the process of hyphal morphogenesis, the crucial impact of hyphal morphology on fermentation production, and traditional control strategies, laying a solid foundation for subsequent research (Cairns et al., 2019b; Lu et al., 2024; Meyer et al., 2021). However, given the complexity and diversity of morphological regulation strategies, the underlying regulatory mechanisms and logical frameworks remain insufficiently clarified. In recent years, the development and maturation of technologies such as efficient genetic editing (Li et al., 2023b), high-throughput screening (Li et al., 2023a), multi-omics sequencing (Yang et al., 2025a, Yang et al., 2025b), and artificial intelligence (Garg, 2025) have provided new tools and highly effective strategies for studying hyphal morphology regulation and elucidating related regulatory mechanisms. Building upon an extensive survey of relevant research reports and integrating the research findings and insights of the author's team, this review first systematically outlines the characteristic morphological developmental features of filamentous fungi and their multi-dimensional effects on industrial fermentation performance. Subsequently, it focuses on analyzing morphology regulation strategies from different perspectives and their underlying logic. Finally, the core of this article concentrated on how to integrate emerging technologies, such as genetic editing, multi-omics, and artificial intelligence, to establish a precise and rational system for hyphal morphology regulation, while also providing an outlook on future research directions. This review aims to provide fresh perspectives and practical strategies for developing filamentous fungal chassis cells suitable for high-efficiency industrial fermentation.