Microbial production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), from lab to the shelf: A review.

Polyhydroxyalkanoates (PHAs) are natural biopolyesters produced by microorganisms that represent one of the most promising candidates for the replacement of conventional plastics due to their complete biodegradability and advantageous material properties which can be modulated by varying their monomer composition. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] has received particular research attention because it can be synthesized based on the same microbial platform developed for poly(3-hydroxybutyrate) [P(3HB)] without much modification, with as high productivity as P(3HB). It also offers more useful mechanical and thermal properties than P(3HB), which broaden its application as a biocompatible and biodegradable polyester. However, a significant commercial disadvantage of P(3HB-co-3HV) is its rather high production cost, thus many studies have investigated the economical synthesis of P(3HB-co-3HV) from structurally related and unrelated carbon sources in both wild-type and recombinant microbial strains. A large number of metabolic engineering strategies have also been proposed to tune the monomer composition of P(3HB-co-3HV) and thus its material properties. In this review, recent metabolic engineering strategies designed for enhanced production of P(3HB-co-3HV) are discussed, along with their current status, limitations, and future perspectives.

Customized valorization of waste streams by Pseudomonas putida: State-of-the-art, challenges, and future trends.

Preventing catastrophic climate events warrants prompt action to delay global warming, which threatens health and food security. In this context, waste management using engineered microbes has emerged as a long-term eco-friendly solution for addressing the global climate crisis and transitioning to clean energy. Notably, Pseudomonas putida can valorize industry-derived synthetic wastes including plastics, oils, food, and agricultural waste into products of interest, and it has been extensively explored for establishing a fully circular bioeconomy through the conversion of waste into bio-based products, including platform chemicals (e.g., cis,cis-muconic and adipic acid) and biopolymers (e.g., medium-chain length polyhydroxyalkanoate). However, the efficiency of waste pretreatment technologies, capability of microbial cell factories, and practicability of synthetic biology tools remain low, posing a challenge to the industrial application of P. putida. The present review discusses the state-of-the-art, challenges, and future prospects for divergent biosynthesis of versatile products from waste-derived feedstocks using P. putida.

Valorization of lignocellulosic biomass for polyhydroxyalkanoate production: Status and perspectives.

With the increasing concerns regarding climate, energy, and plastic crises, bio-based production of biodegradable polymers has become a dire necessity. Significant progress has been made in biotechnology for the production of biodegradable polymers from renewable resources to achieve the goal of zero plastic waste and a net-zero carbon bioeconomy. In this review, an overview of polyhydroxyalkanoate (PHA) production from lignocellulosic biomass (LCB) was presented. Having established LCB-based biorefinery with proper pretreatment techniques, various PHAs could be produced from LCB-derived sugars, hydrolysates, and/or aromatic mixtures employing microorganisms. This provides a clue for addressing the current environmental crises because "biodegradable polymers" could be produced from one of the most abundant resources that are renewable and sustainable in a "carbon-neutral process". Furthermore, the potential future of LCB-to-non-natural PHA production was discussed with particular reference to non-natural PHA biosynthesis methods and LCB-derived aromatic mixture biofunnelling systems.

Consolidated microbial production of four-, five-, and six-carbon organic acids from crop residues: Current status and perspectives.

The production of platform organic acids has been heavily dependent on petroleum-based industries. However, petrochemical-based industries that cannot guarantee a virtuous cycle of carbons released during various processes are now facing obsolescence because of the depletion of finite fossil fuel reserves and associated environmental pollutions. Thus, the transition into a circular economy in terms of the carbon footprint has been evaluated with the development of efficient microbial cell factories using renewable feedstocks. Herein, the recent progress on bio-based production of organic acids with four-, five-, and six-carbon backbones, including butyric acid and 3-hydroxybutyric acid (C4), 5-aminolevulinic acid and citramalic acid (C5), and hexanoic acid (C6), is discussed. Then, the current research on the production of C4-C6 organic acids is illustrated to suggest future directions for developing crop-residue based consolidated bioprocessing of C4-C6 organic acids using host strains with tailor-made capabilities.

Microbial cell factories for the production of three-carbon backbone organic acids from agro-industrial wastes.

At present, mass production of basic and valuable commodities is dependent on linear petroleum-based industries, which ultimately makes the depletion of finite natural reserves and accumulation of non-biodegradable and hazardous wastes. Therefore, an ecofriendly and sustainable solution should be established for a circular economy where infinite resources, such as agro-industrial wastes, are fully utilized as substrates in the production of target value-added chemicals. Hereby, recent advances in metabolic engineering strategies and techniques used in the development of microbial cell factories for enhanced production of three-carbon platform chemicals such as lactic acid, propionic acid, and 3-hydroxypropionic acid are discussed. Further developments and future perspectives in the production of these organic acids from agro-industrial wastes from the dairy, sugar, and biodiesel industries are also highlighted to demonstrate the importance of waste-based biorefineries for organic acid production.

A shortcut to carbon-neutral bioplastic production: Recent advances in microbial production of polyhydroxyalkanoates from C1 resources.

Since the 20th century, plastics that are widely being used in general life and industries are causing enormous plastic waste problems since improperly discarded plastics barely degrade and decompose. Thus, the demand for polyhydroxyalkanoates (PHAs), biodegradable polymers with material properties similar to conventional petroleum-based plastics, has been increased so far. The microbial production of PHAs is an environment-friendly solution for the current plastic crisis, however, the carbon sources for the microbial PHA production is a crucial factor to be considered in terms of carbon-neutrality. One­carbon (C1) resources, such as methane, carbon monoxide, and carbon dioxide, are greenhouse gases and are abundantly found in nature and industry. C1 resources as the carbon sources for PHA production have a completely closed carbon loop with much advances; i) fast carbon circulation with direct bioconversion process and ii) simple fermentation procedure without sterilization as non-preferable nutrients. This review discusses the biosynthesis of PHAs based on C1 resource utilization by wild-type and metabolically engineered microbial host strains via biorefinery processes.

Development of a Novel Controlled-Release Tablet of Pregabalin: Formulation Variation and Pharmacokinetics in Dogs and Humans.

BACKGROUND: Novel three-layered (TL) tablet systems were compared with both monolithic matrix (MM) formulations and a commercial immediate-release (IR) capsule to develop once-a-day (OAD) pregabalin tablets. METHODS: The physical properties of the TL tablets, including dissolution and swelling rates, were compared with those of the MM tablets and the pharmacokinetic parameters of the TL tablet were compared with those of an IR capsule in beagles and humans. RESULTS: Our results indicated that the same amount of a hydrophilic polymer in the formulations had similar dissolution profiles at 12 h, regardless of the tablet geometry. However, the degree of tablet swelling differed, with larger amounts of polymer in the tablets showing a greater degree of swelling. In addition, TL tablets swelled more rapidly compared with MM tablets. For the pharmacokinetic study of the TL tablet, the beagles demonstrated absorption results similar to those of an IR capsule, whereas the humans demonstrated low total absorption compared with an IR capsule. The time of the peak plasma concentration at 6 h in the fed state of humans coincided with the results of the study on beagles. CONCLUSION: The novel TL tablet system of pregabalin may prove to be helpful in developing improved formulations with better continuous drug absorption for OAD administration.