Recent Advances of Controllable Production of PHA Biosynthesis in Chain Length, Monomers and Special Functional...

Realizing the full potential of polyhydroxyalkanoates (PHAs) as sustainable alternatives to conventional plastics necessitates, a fundamental transformation in biomanufacturing should be made, from the production of heterogeneous polymer mixtures to the deliberate synthesis of well-defined, tailor-made biopolymers with predictable physicochemical properties. This review delineates a comprehensive framework for achieving controllable PHA biosynthesis, where the field is evolving from a phase of empirical discovery to one of precision-driven design. It underscores the need for seamless integration of genetic engineering, enzyme evolution, and bioprocess control. We systematically analyze recent advances that enable precise regulation of polymer architecture, including control over chain-length distribution, selective monomer incorporation, and the integration of functional moieties within the polymer backbone. By synthesizing developments in genetic circuit engineering, enzyme optimization, and adaptive fermentation strategies, we highlight emerging approaches for designing PHAs with tunable mechanical and functional attributes suited for specialized, high-value applications. Finally, the review identifies persistent challenges and potentials related to scalability, purity, process integration and AI-guided enzymes design, etc., emphasizing the need for interdisciplinary collaboration to bridge the divide between metabolic precision and industrial feasibility.