Air‐Mediated Biomimetic Synthesis of Polyhydroxyalkanoate with C4 Diol

Poly(4-hydroxybutyrate) (P4HB) is a high-performance, well-recyclable, and biodegradable polyhydroxyalkanoate (PHA). However, conventional bioproduction of homopolymeric P4HB involves complex and costly processes with C4 feedstocks, particularly 1,4-butanediol (BDO), and enzyme-coenzyme systems in genetically engineered bacteria. An alternative extracellular chemical route utilizing aerial oxidation of BDO offers cost and energy benefits but struggle with conversion efficiency. Inspired by efficient intracellular oxidation of primary alcohols, we propose a ruthenium-phosphine synergistic catalytic system that mimics enzyme-coenzyme functionality. This system effectively catalyzed the air-mediated, solvent-free oxidation of BDO to produce γ-butyrolactone (γ-BL) and oligomeric P4HB, with a space-time yield (10.37 g [γ-BL unit] g^-1 catalyst h^-1) surpassing the values (<5.5) of previous approaches. The oligomer-containing products were reversibly converted to γ-BL and then to P4HB (28.9 kDa) via ring-opening polymerization, exceeding reported values (<16 kDa). This study provides the potential for large-scale synthesis of high-value PHAs from diverse non-grain-based diols, offering economic and environmental advantages.