Poly(4-Hydroxybutyrate): Current State and Perspectives.

Camila Utsunomia,Qun Ren,Manfred Zinn

doi:10.3389/fbioe.2020.00257

Abstract

By the end of 1980s, for the first time polyhydroxyalkanoate (PHA) copolymers with incorporated 4-hydroxybutyrate (4HB) units were produced in the bacterium Cupriavidus necator (formally Ralstonia eutropha) from structurally related carbon sources. After that, production of PHA copolymers composed of 3-hydroxybutyrate (3HB) and 4HB [P(3HB-co-4HB)] was demonstrated in diverse wild-type bacteria. The P4HB homopolymer, however, was hardly synthesized because existing bacterial metabolism on 4HB precursors also generate and incorporate 3HB. The resulting material assumes the properties of thermoplastics and elastomers depending on the 4HB fraction in the copolyester. Given the fact that P4HB is biodegradable and yield 4HB, which is a normal compound in the human body and proven to be biocompatible, P4HB has become a prospective material for medical applications, which is the only FDA approved PHA for medical applications since 2007. Different from other materials used in similar applications, high molecular weight P4HB cannot be produced via chemical synthesis. Thus, aiming at the commercial production of this type of PHA, genetic engineering was extensively applied resulting in various production strains, with the ability to convert unrelated carbon sources (e.g., sugars) to 4HB, and capable of producing homopolymeric P4HB. In 2001, Metabolix Inc. filed a patent concerning genetically modified and stable organisms, e.g., Escherichia coli, producing P4HB and copolymers from inexpensive carbon sources. The patent is currently hold by Tepha Inc., the only worldwide producer of commercial P4HB. To date, numerous patents on various applications of P4HB in the medical field have been filed. This review will comprehensively cover the historical evolution and the most recent publications on P4HB biosynthesis, material properties, and industrial and medical applications. Finally, perspectives for the research and commercialization of P4HB will be presented.

Highlights

In 1926, the first polyhydroxalkanoate (PHA), poly(3-hydroxybutyrate) (P3HB) (Figure 1), was discovered by the French scientist Maurice Lemoigne during his work with the bacterium Bacillus megaterium (Lemoigne, 1926)
The efficient incorporation of 4HB by C. acidovorans JCM10181 was shown to depend on the 4HB precursor supplied (i.e., 4-hydroxybutyric acid, 1,4-BDO, and γ-butyrolactone), among which feeding 4-hydroxybutyric acid resulted in polymer with the highest 4HB fraction (96 mol%) and accumulation up to 25% of the dry cell weight (Lee et al, 2004)
This study indicated that 4HB-CoA is likely to be generated from succinylCoA, an intermediary of the tricarboxylic acid cycle (TCA)

Summary

INTRODUCTION

In 1926, the first polyhydroxalkanoate (PHA), poly(3-hydroxybutyrate) (P3HB) (Figure 1), was discovered by the French scientist Maurice Lemoigne during his work with the bacterium Bacillus megaterium (Lemoigne, 1926). The high production cost of which approximately 50% are attributed to the precursor substrates, commonly pure sugars and fatty acids, limits the bulk application of PHAs (Koller et al, 2017). These microbial polyesters are estimated to be 3–4 times more expensive than synthetic plastics, such as polypropylene and polyethylene, and exhibit more inconsistent material properties (Kourmentza et al, 2017; Zhang et al, 2018). The products of PHA degradation are CO2 and H2O, and CO2 and methane when it occurs aerobically and anaerobically, respectively Environmental conditions, such as temperature and pH, and PHA properties, likewise monomer type, molecular weight, crystallinity, and surface area, directly influence the degradation rate.

Methods for separation and purifying polyhydroxyalkanoates

Findings

CONCLUSION