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[4Ferm-03]Dynamic feeding strategies for scalable polyhydroxyalkanoates production from lactic acid

○Lijun Luo1, Nirakar Pradhan1 (1. Hong Kong Baptist University (Hong Kong))
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Keywords:

Polyhydroxyalkanoates (PHA),Feeding strategies,Lactic acid,Biopolymer,Cupriavidus necator

Polyhydroxyalkanoates (PHA) are a family of biopolymers that are promising sustainable alternatives to conventional plastics. The waste valorization underpins the circular economy, and lactic acid (LA), which can be efficiently produced from such waste streams, is an attractive carbon source for PHA synthesis. However, a major technical hurdle is that elevated LA concentrations during fed-batch fermentation can inhibit cell growth and reduce PHA productivity, creating a bottleneck for industrial-scale production. Therefore, it is necessary to develop a feeding strategy that tightly controls the LA concentration below inhibitory levels.

In this study, we designed and evaluated three scalable feeding strategies for PHA production using Cupriavidus necator and LA as the sole carbon source. Our goal was to balance rapid cell growth with high-volume PHA accumulation by preventing substrate toxicity. These strategies were: (i) pH-stat feeding, which cleverly uses LA as both a pH-control agent and carbon source; (ii) continuous feeding, which provides a steady, low-rate supply of LA; and (iii) a combined two-stage approach that leverages pH-stat feeding during the initial growth phase and switches to continuous feeding during the PHA accumulation phase.

All three strategies successfully maintained LA below inhibitory levels and enabled high PHA accumulation. Notably, our results showed a maximum cell dry weight (CDW) of ~23 g/L, with a remarkable PHA content of nearly 70% of CDW and a final PHA concentration of about 16 g/L. The overall PHA yield was over 0.5 g PHA/g of carbon from LA, demonstrating highly efficient carbon conversion. These results demonstrate that controlling LA availability through a rationally designed, dynamic feeding strategy can effectively mitigate substrate toxicity while delivering high PHA accumulation and yield. This work provides a robust and scalable framework for the industrial bioproduction of PHA from waste-derived lactic acid, advancing the economic feasibility of bioplastics.

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