Pilot Scale‐up of Poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) Production by Halomonas bluephagenesis via Cell Growth Adapted Optimization Process

Poly(3‐hydroxybutyrate‐ co ‐4‐hydroxybutyrate), P(3HB‐ co ‐4HB), is one of the most valuable biopolymers because of its flexible mechanical properties. In this study, the goal is to establish a scaled‐up process of low cost P(3HB‐ co ‐4HB) from a 7.5‐L fermentor to 1‐ and 5‐m 3 industrial bioreactors, respectively, using Halomonas bluephagenesis TD40 grown on glucose, γ ‐butyrolactone, and waste corn steep liquor (CSL) as substrates, under open non‐sterile and fed‐batch or continuous conditions. The non‐sterile process enables the energy reduction for less steam consumption. Moreover, waste gluconate is successfully utilized to replace glucose as a carbon source for cell growth and PHA accumulation in 7.5‐L fermentor, which opens the possibility of 60% of raw material cost reduction for recycling the waste resources. A mathematical model and rational calculation is established to help guide the feeding strategy and scale‐up, respectively, leading to 100 g L −1 cell dry weight (CDW) containing 60.4% P(3HB‐ co ‐mol 13.5% 4HB) after 36 h of growth in the 5 m 3 vessel. An even higher P(3HB‐ co ‐4HB) content of 74% is achieved by decreasing the use of waste CSL. A stable and continuous open process for efficient low‐cost production of P(3HB‐ co ‐4HB) is successfully developed coupling fermentation with the downstream extraction processing.