Bioreactor Operating Strategies for Improved Polyhydroxyalkanoate (PHA) Productivity

Abstract

Microbial polyhydroxyalkanoates (PHAs) are promising biodegradable polymers that may alleviate some of the environmental burden of petroleum-derived polymers. The requirements for carbon substrates and energy for bioreactor operations are major factors contributing to the high production costs and environmental impact of PHAs. Improving the process productivity is an important aspect of cost reduction, which has been attempted using a variety of fed-batch, continuous, and semi-continuous bioreactor systems, with variable results. The purpose of this review is to summarize the bioreactor operations targeting high PHA productivity using pure cultures. The highest volumetric PHA productivity was reported more than 20 years ago for poly(3-hydroxybutryate) (PHB) production from sucrose (5.1 g L−1 h−1). In the time since, similar results have not been achieved on a scale of more than 100 L. More recently, a number fed-batch and semi-continuous (cyclic) bioreactor operation strategies have reported reasonably high productivities (1 g L−1 h−1 to 2 g L−1 h−1) under more realistic conditions for pilot or industrial-scale production, including the utilization of lower-cost waste carbon substrates and atmospheric air as the aeration medium, as well as cultivation under non-sterile conditions. Little development has occurred in the area of fully continuously fed bioreactor systems over the last eight years.

Development of High Cell Density Cultivation Strategies for Improved Medium Chain Length Polyhydroxyalkanoate Productivity Using Pseudomonas putida LS46

“…It is important to point out that the main contribution of this work was to show the effects of low-DO environments in HCD fed-batch cultivations under different feeding strategies, and not necessarily to maximize overall Q v using techniques to keep DO in excess. Although those are worthwhile pursuits, they have been extensively explored in the literature, but have not necessarily been replicated in larger scale bioreactors [22]. Regardless of how much the oxygen transfer rate might be improved, at some point microaerophilic conditions will persist beyond a certain cell density.…”

“…While these results are indeed impressive, many of these studies were performed at bench-scale and used an aeration medium with enriched oxygen content, which can add significant costs in a large-scale setting. A recent survey of scale-up operations in PHA production pointed out that productivities reported for scaled-up operations have, for some time, been lagging behind those achieved in the lab [22]. This discrepancy is at least partly attributable to poor mass transfer characteristics within large-scale bioreactors, especially when it comes to maintaining dissolved oxygen (DO) in aerobic bioprocesses [23,24].…”

Switching from petro-plastics to microbial polyhydroxyalkanoates (PHA): the biotechnological escape route of choice out of the plastic predicament?

“…PHA production under controlled conditions, especially on a larger scale, is typically carried out in bioreactors (77,78); such bioreactors (previously also known as "fermenters") can be operated in different modes, such as batch (substrate feed only at the beginning, product harvest only at the end of the The EuroBiotech Journal process), fed-batch (repeated substrate supply according to substrate analysis, harvest only at the end), and continuous (permanent supply of substrates and products harvest) setups. In this context, PHA biosynthesis has to be understood as a multiphase process, because product (PHA) accumulation as a intracellular secondary metabolite is typically not coupled to the preceding phase of microbial growth (formation of active biomass).…”

“…Therefore, both feeding strategy and bioreactor operation mode need to be carefully adapted to the selected production strain, substrate, and kinetics of growth and product formation (79). Traditional PHA production setups operated in batch (80), repeated batch ("fill-and-empty" or "drain-and-fill" cultivation) (81), fed-batch (82), or cyclic fed-batch mode (83) often show unsatisfactory control of PHA composition, and are often characterized by modest volumetric productivity (77,78).…”

Effect of different fermentation strategies on Bacillus thuringiensis cultivation and its toxicity towards the bagworm, Metisa plana Walker (Lepidoptera: Psychidae)

“…A mixture of Bt spores and crystals can be produced using different modes of cultivation (Aronson and Yechiel 2001). Many researchers have reported the use of fed-batch cultivation for the production of high-density cell culture (Stanbury et al 2003;Krause et al 2010;Warren et al 2018). The maximum cell concentration obtained in fed-batch cultivation (53.7 g/l) of Bt subspecies kurstaki was ninefold higher as compared to that obtained in batch cultivation (5.9 g/l) (Liu et al 1994).…”