Engineering Native and Synthetic Pathways in Pseudomonas putida for the Production of Tailored Polyhydroxyalkanoates

Abstract

Growing environmental concern sparks renewed interest in the sustainable production of (bio)materials that can replace oil‐derived goods. Polyhydroxyalkanoates (PHAs) are isotactic polymers that play a critical role in the central metabolism of producer bacteria, as they act as dynamic reservoirs of carbon and reducing equivalents. PHAs continue to attract industrial attention as a starting point toward renewable, biodegradable, biocompatible, and versatile thermoplastic and elastomeric materials. Pseudomonas species have been known for long as efficient biopolymer producers, especially for medium‐chain‐length PHAs. The surge of synthetic biology and metabolic engineering approaches in recent years offers the possibility of exploiting the untapped potential of Pseudomonas cell factories for the production of tailored PHAs. In this article, an overview of the metabolic and regulatory circuits that rule PHA accumulation in Pseudomonas putida is provided, and approaches leading to the biosynthesis of novel polymers (e.g., PHAs including nonbiological chemical elements in their structures) are discussed. The potential of novel PHAs to disrupt existing and future market segments is closer to realization than ever before. The review is concluded by pinpointing challenges that currently hinder the wide adoption of bio‐based PHAs, and strategies toward programmable polymer biosynthesis from alternative substrates in engineered P. putida strains are proposed.

From Residues to Added-Value Bacterial Biopolymers as Nanomaterials for Biomedical Applications

“…Furthermore, several recombinant strains have been developed to produce PHA. Despite the fact that the most common substituent groups found in PHA monomers are aliphatic chains, over 150 different monomer constituents have been described [31]. They are often classified as short-chain-length PHA (scl-PHA) or medium-chain-length PHA (mcl-PHA) based on monomer size, with 3-5 or 6-14 carbon units, respectively.…”

“…They are often classified as short-chain-length PHA (scl-PHA) or medium-chain-length PHA (mcl-PHA) based on monomer size, with 3-5 or 6-14 carbon units, respectively. The type of PHA synthesized depends upon the type of PHA synthase (PhaC), which can accept precursors of a certain carbon length, as well as the substrate employed and the metabolic and regulatory networks in each species [31].…”

“…The potential to edit and redirect the cell system using metabolic and genetic engineering tools combined with bioprocess engineering strategies has led to the creation of rationally designed PHAs for targeted applications [29,31]. It is now possible to obtain PHA homopolymers, random and block copolymers, or functional and graft PHA polymers by controlling the carbon flow by manipulating the bacterial PHA synthesis metabolism [171,172].…”

“…Furthermore, the ability of some bacteria to incorporate R-HA-CoA, bearing functional groups from related substrates, gives rise to great monomeric structural diversification by both biosynthetic and postbiosynthetic chemical modifications [31]. Related carbon sources have been used to obtain PHAs containing double or triple bonds [176], monohalogenated [79], aromatic [73,74], thioether [177], thioester [77], cyano, or nitro [76] side groups, among others.…”

Post-Transcriptional Control in the Regulation of Polyhydroxyalkanoates Synthesis

“…Therefore, to break the plastic wave, bio-based and biodegradable alternatives to synthetic plastics should be considered [ 9 , 10 ], especially with the drastic increase in plastic pollution due to the current COVID-19 pandemic [ 11 , 12 ]. However, the elevated cost of industrial procedures and lack of significant large-scale production [ 13 , 14 , 15 , 16 ], together with the availability of appropriated carbon sources, have limited faster progress in these processes and consequently greater market penetration [ 17 , 18 ].…”