Strategies for Large-scale Production of Polyhydroxyalkanoates

Polyhroxyalkanoates (PHAs) are macromolecular storage polyesters produced by metabolic transformation of carbon sources by microorganisms, under nutrient limiting conditions. The latter involves excess of carbon source and limiting concentrations of at least one other essential nutrient, such as nitrogen, phosphorous, and/or sulphur.1 PHA accumulation as intracellular carbon and energy reserves can be rationalised due to their oxidized state and consequent high calorific value of >20 KJ g–1.2 The ever increasing popularity of PHAs is based on their biodegradable and biocompatible nature along with the possibility of tailored molecular structure and/or composition, which makes them highly versatile candidate materials for a range of different applications, including bulk and medical.3,4 This has led to the development of more than 150 different types of biotechnologically produced PHAs to date.5 PHAs offer several distinct advantages over other popular biopolymers such as poly-L-lactic acid (PLLA) or starch-based polymers e.g., starch-polyethylene. PHA degradation mechanism involves surface erosion rather than bulk degradation reported for PLLA. This allows a more predictable degradation profile of PHA-based medical products than PLLA. In addition, PHAs have reduced immune response due to lower acidity of their degradation products as compared to the toxicity resulting from a huge accumulation of lactic acid generated by PLLA degradation. The latter leads to complications in medical applications.6 The monomeric composition also affects the degradation rate of PHAs. Thus, the possibility of a tailored composition of PHAs provides a means to control their degradation at a desired rate (short or extended period of time) depending upon the application.7 Both in-vitro and in-vivo tests have proved PHAs to be biocompatible with bone, cartilage, blood and various other cell lines. Their biocompatibility has been reviewed in detail by Valappil et al.8 Other polymers, such as starch, exhibit unsatisfactory mechanical properties and difficult processing.9 Thus, the lack of variability in structure, extensive material properties, and controlled degradation for PLLA or starch-based polymers makes them less attractive than PHAs. Several microorganisms, including both native and recombinant strains, have been employed for PHA production. Industrial production processes for PHAs have generally been developed using Gram negative strains, such as Cupriavidus necator and Alcaligenes latus, mainly due to the relatively high PHA yields offered by them and the ability of some strains to synthesize PHAs under nutrient non-limiting conditions.10–11 However, huge efforts have also been directed towards process development based on Gram positive strains such as Bacillus sp. and Corynebacterium glutamicum. Their primary advantage is the absence of the lipopolyStrategies for Large-scale Production of Polyhydroxyalkanoates