phaC1

phaC1 is a gene encoding a polyhydroxyalkanoate (PHA) synthase, an enzyme that catalyzes the polymerization of hydroxyalkanoate CoA thioesters into polyhydroxyalkanoate granules stored in many bacteria under nutrient imbalance. In several Pseudomonas species, including some widely studied strains, phaC1 is part of a duplicated pair with phaC2, encoding two distinct PHA synthases of class II. These enzymes drive the formation of PHA polymers, with differences in substrate range and regulatory control between the two synthases.

The phaC1 gene is typically located within a PHA biosynthesis operon that may include phaA (β-ketoacyl-CoA thiolase) and phaB (3-hydroxyacyl-CoA dehydrogenase). Expression of phaC1 is influenced by carbon and nitrogen availability and other regulatory factors, with PHA accumulation occurring when carbon is abundant but nutrient-limited, allowing cells to store carbon and energy as intracellular granules.

Mechanistically, PhaC1 operates via a thiolase-type reaction in which a catalytic cysteine forms a covalent intermediate with the growing PHA chain. Polymerization proceeds through successive additions of hydroxyacyl-CoA monomers, and the enzyme is commonly associated with the surface of PHA granules, where it coordinates with granule-associated proteins to facilitate polymer growth and granule formation. Structural and kinetic variations between phaC1 and phaC2 contribute to different substrate specificities and polymer characteristics, which can be exploited in metabolic engineering.

Applications of studies on phaC1 include strategies to optimize microbial production of biodegradable PHAs for industrial use, by tuning expression, substrate supply, and enzyme specificity.