Enhanced production of polyhydroxyalkanoate with manipulable and reproducible 3-hydroxyvalerate fraction by high alcohol tolerant Cupriavidus malaysiensis USMAA2-4 transformant.

The domination of high-cost organic acids over other 3-hydroxyvalerate (3HV) precursors due to the wide preference among polyhydroxyalkanoates (PHA)-producing bacteria has limited the development of diverse poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] production processes. 1-pentanol is a low-cost 3HV precursor but is rarely employed due to the relatively low tolerance among PHA-producing bacteria. This study demonstrated P(3HB-co-3HV) production with manipulable and reproducible 3HV composition and 3HV yield from palm olein and 1-pentanol. Cupriavidus malaysiensis USMAA2-4ABH16 is the transformant strain with acquired lipase genes that retains the high tolerance towards 1-pentanol of its wild-type, with a preference for 1-pentanol over valeric acid indicated by the sixfold higher 3HV yield than that from valeric acid. C. malaysiensis USMAA2-4ABH16 was able to tolerate up to 0.15 wt% C 1-pentanol. Upon optimization using response surface methodology, 0.41‒0.52 g/g P(3HB-co-3HV) yield and 72‒89 wt% PHA content was achieved for 7, 9, 12 and 16 mol% 3HV, with 3HV yields of 0.30 g/g, 0.26 g/g, 0.23 g/g and 0.23 g/g, respectively. Up-scaling batch production by adopting the optimized concentrations of substrates for 12 mol% 3HV resulted in reproducible 3HV composition and 3HV yield on a 120-fold larger scale. The P(3HB-co-12 mol% 3HV) produced displayed higher flexibility than polypropylene and P(3HB-co-3HV) produced from different carbon sources. C. malaysiensis USMAA2-4ABH16 could be practically applicable for sustainable and economically feasible P(3HB-co-3HV) production on an industrial scale from used palm olein with relatively similar oleic acid content with palm olein and 1-pentanol, with higher 3HV compositions achievable through fed-batch strategies owing to its high 1-pentanol tolerance.

A Critical Review on the Economically Feasible and Sustainable Poly(3-Hydroxybutyrate-co-3-hydroxyvalerate) Production from Alkyl Alcohols.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)) is the most studied short-chain-length polyhydroxyalkanoates (PHA) with high application importance in various fields. The domination of high-cost propionate and valerate over other 3-hydroxyvalerate (3HV) precursors owing to their wide preference among PHA-producing bacteria has hindered the development of diverse production processes. As alkyl alcohols are mainly produced from inexpensive starting materials through oxo synthesis, they contribute a cost-effective advantage over propionate and valerate. Moreover, alkyl alcohols can be biosynthesized from natural substrates and organic wastes. Despite their great potential, their toxicity to most PHA-producing bacteria has been the major drawback for their wide implementation as 3HV precursors for decades. Although the standard PHA-producing bacteria Cupriavidus necator showed promising alcohol tolerance, the 3HV yield was discouraging. Continuous discovery of alkyl alcohols-utilizing PHA-producing bacteria has enabled broader choices in 3HV precursor selection for diverse P(3HB-co-3HV) production processes with higher economic feasibility. Besides continuous effort in searching for promising wild-type strains, genetic engineering to construct promising recombinant strains based on the understanding of the mechanisms involved in alkyl alcohols toxicity and tolerance is an alternative approach. However, more studies are required for techno-economic assessment to analyze the economic performance of alkyl alcohol-based production compared to that of organic acids.

Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges.

Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers' natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.