Current Advances towards 4-Hydroxybutyrate Containing Polyhydroxyalkanoates Production for Biomedical Applications.

Jing Han,Ruchira Mitra,Hua Xiang

doi:10.3390/molecules26237244

Abstract

Polyhydroxyalkanoates (PHA) are polyesters having high promise in biomedical applications. Among different types of PHA, poly-4-hydroxybutyrate (P4HB) is the only polymer that has received FDA approval for medical applications. However, most PHA producing microorganisms lack the ability to synthesize P4HB or PHA comprising 4-hydroxybutyrate (4HB) monomer due to their absence of a 4HB monomer supplying pathway. Thus, most microorganisms require supplementation of 4HB precursors to synthesize 4HB polymers. However, usage of 4HB precursors incurs additional production cost. Therefore, researchers have adopted strategies to reduce the cost, such as utilizing low-cost substrate as well as constructing 4HB monomer supplying pathways in microorganisms. We herein summarize the biomedical applications of P4HB, the natural producers of 4HB polymer, and the various strategies that have been applied in producing 4HB polymers in non-4HB producing microorganisms. It is expected that the readers would gain a vivid idea on the different strategic developments in the field of 4HB polymer production.

Highlights

As the global concerns about environmental sustainability is rising, bioplastics are gaining increasing importance as a viable alternative to petrochemical-based plastics [1].Bioplastics are environmentally friendly, biodegradable materials derived from renewable sources
To commercialize the use of P4HB and make it available for use in daily lives, it is important to curb down the production cost of P4HB
In the shake flasks containing LB medium supplemented with glucose, E. coli with no phaP gene synthesized only 12.13 wt% (CDW) P4HB whereas individual phaP expression increased the content to

Summary

Introduction

As the global concerns about environmental sustainability is rising, bioplastics are gaining increasing importance as a viable alternative to petrochemical-based plastics [1]. Properties of PHA polymers somehow depend on their monomer composition. By changing the monomer type and composition, PHA with favorable material properties can be achieved [4]. Researchers are continuously engrossed in developing various strategies to realize P4HB synthesis in microbes, and to achieve 4HB-containing polymers with tailor-made 4HB content. The present review discusses the various research techniques of P4HB or its copolymer synthesis. We have presented the natural producers of 4HB polymer and the 4HB synthesis pathway. We have categorically divided the different approaches of obtaining 4HB polymers in nonnatural 4HB producers. These include precursor supplementation, utilization of low-cost substrates, optimization of cultivation parameters, and metabolic engineering to construct 4HB synthesis pathways

Medical Application of P4HB

Microbial Synthesis of P4HB

Natural 4HB Polymer Producers and 4HB-CoA Supplying Pathway

Precursor Supplementation to Yield 4HB Copolymers

Microbial Synthesis of 4HB Terpolymer

Utilization of Low-Cost Substrate for 4HB Polymer Synthesis

Cultivation Parameters Affecting 4HB Polymer Synthesis

Metabolic Engineering to Synthesize 4HB Polymers

Synthesis of 4HB Polymer in Other Microbes

Findings

Conclusion and Future Perspectives