Macroalgae (also known as seaweeds) are multicellular, marine algae that are a promising, non-terrestrial resource vital for the blue bioeconomy. Macroalgae offer rapid growth up to 10 % daily without competing for freshwater, fertilizers, or arable land [1]. Beyond resource conservation, macroalgae serve a critical ecological function in marine carbon fixation and potential sequestration, making them a vital component in climate change mitigation efforts [2]. Their rich, inherent biochemical composition, including complex polysaccharides (alginate, carrageenan, and agar), proteins, and unique bioactive lipids, presents a valuable resource across culinary, pharmaceutical, cosmetic, and material industries [3].

Despite this dual environmental and commercial benefit, the macroalgal industry faces significant hurdles. The rigid, intricate cell wall structure of macroalgae necessitates intensive and often harsh pretreatment methods, resulting in high processing costs and potential degradation of sensitive, high-value compounds. Furthermore, the overall economic viability is restricted by the typically low concentration of desired compounds, such as omega-3 lipids, and the high cost associated with large-scale cultivation. Overcoming these limitations necessitates a fundamental shift toward a biotechnological paradigm and a strategy that maximizes total biomass value. While enzymatic and microbial methods are often explored separately, a comprehensive synthesis of how their synergistic integration within a cascading circular biorefinery model is required to define a techno-economically feasible roadmap for commercial success.

This review focuses on the integration of enzyme and microbial biotechnology as the essential tools for achieving selective extraction and cascading valorization within a circular bioeconomy model. Enzymes offer specificity and mild operating conditions, which are crucial for extracting pure, high-value components. Meanwhile, microbial platforms efficiently convert the residual biomass into useful bulk products, thereby maximizing the utility of the biologically fixed carbon. The integration of molecular omics provides the necessary foundation for engineering these biological systems and helps in the identification of novel enzymes. We analyze the current state of these biotechnologies, discuss their role in establishing robust biorefineries, and outline how the framework supports global climate change mitigation efforts. Therefore, life cycle assessment (LCA) is considered a critical tool for validating the sustainability claims of the biorefinery approach, including the quantification of its carbon sequestration implications. This review does not just summarize existing LCAs; it conducts a critical synthesis of methodologies to establish an essential framework for future studies, ensuring consistent assessment of the unique challenges inherent to macroalgal valorization.