Molecular engineering of single-cell proteins for precision functional food design: Linking cellular architecture, protein structure, digestibility, and techno-functional performance

Abstract

Single-cell proteins (SCPs) are promising sustainable protein platforms; however, their successful translation into next-generation functional food ingredients depends not only on protein abundance but also on molecular architecture controlling digestibility, bioaccessibility, and techno-functional performance. This review critically evaluates how molecular engineering strategies, including metabolic engineering, synthetic biology, protein design, and cell-wall remodeling, regulate SCP structure-function relationships for improved nutritional and technological properties. Recent advances demonstrate significant improvements in SCP quality, such as a 31% increase in amino acid content in engineered Saccharomyces cerevisiae and enhanced mycoprotein performance following cell-wall optimization, increasing protein content from 47.84% to 71.22%, solubility from 5.57% to 79.60%, and in vitro digestibility from 75.17% to 86.39%. However, protein enrichment alone does not guarantee improved functionality, as secondary structure composition, aggregation behavior, surface properties, and cell-wall organization critically determine enzyme accessibility, amino acid release, and food processing performance. The review highlights quantitative and mechanistic links between engineered molecular features and key techno-functional properties, including solubility, emulsification, foaming, gelation, and thermal stability, enabling SCP applications in dairy alternatives, meat analogues, bakery products, and beverages. Although engineered SCPs may offer opportunities for generating bioactive peptides and modulating gut microbiota-related functions, current evidence largely derives from native SCP biomass, and the specific effects of molecular engineering remain unclear. Furthermore, safety-by-design approaches are required to assess potential changes in allergenic epitopes, immunogenicity, and regulatory acceptance. Major challenges include limited standardized structure-function evaluation, insufficient integration of multi-omics with food functionality, metabolic trade-offs during engineering, and inadequate clinical validation. Future progress will require integration of synthetic biology, AI-assisted design, precision fermentation, and advanced nutritional assessment to develop predictable, safe, and scalable SCP-based functional food ingredients.