Oleaginous yeasts, particularly Yarrowia lipolytica, are increasingly used as microbial platforms for producing lipids and other value-added compounds from renewable feedstocks. Their biotechnological utility derives from active lipid metabolism, broad substrate flexibility, and expanding engineering tools, but efficient production requires transcriptional programs that match changing metabolic states during fermentation. Because carbon flux is redistributed across growth, nutrient limitation, lipid accumulation, and production phases, static constitutive expression is often insufficient for optimal pathway performance. Promoter engineering therefore provides a key strategy to control expression strength, timing, and responsiveness in oleaginous yeasts. This review summarizes the metabolic basis of phase-dependent gene expression demand, examines constitutive, inducible, and dynamic promoter systems, and discusses how machine learning can support promoter prediction and design. Current challenges, including limited host-specific datasets, context dependence, and uncertain robustness to scale-up, are also discussed. These advances provide a basis for more precise and scalable engineering of oleaginous yeast cell factories.
Akhmad Awaludin Agustiar, Zewei Lu, Dianqi Yang et al.· Biotechnology Advances· 0 citations
The escalating global population and the environmentally inefficient nature of livestock-based protein production are intensifying demand for sustainable and scalable protein alternatives. Microbial biosynthesis, employing engineered cell factories, represents a pivotal strategy for producing functional proteins with a reduced ecological footprint. This review comprehensively examines the biosynthesis of alternative proteins (APs) via microbial precision fermentation, encompassing diverse categories including coloring proteins, flavoring and taste proteins, structuring and texturizing proteins, nutritional and functional proteins, food processing and enabling proteins, and special functional proteins. Enabling technologies, from fermentation feedstock and microbial host selection to genome/metabolic engineering, bioprocess optimization via response surface methodology/artificial neural networks, and downstream purification, are critically analyzed. Emerging strategies demonstrate substantial progress in enhancing microbial titers, achieving functional mimicry, and advancing regulatory readiness. However, persistent challenges include precise flavor replication, nutritional completeness, and food safety concerns such as allergenicity and process contaminants. Potential solutions, including advanced metabolic engineering, refined protein extraction, biocontainment strategies, and transparent regulatory frameworks, are discussed. By integrating technological innovation with targeted application mapping and regulatory foresight, this review outlines a roadmap toward scalable, safe, and functionally robust microbial AP platforms, thereby contributing to the transition toward a sustainable food system.
Zewei Lu, Zhuoer Chen, Dianqi Yang et al.· Comprehensive Reviews in Foo...· 0 citations