Engineering microbial chemical factories to produce renewable "biomonomers"

Abstract

By applying metabolic engineering tools and strategies to engineer synthetic enzyme pathways, the number and diversity of commodity and specialty chemicals that can be derived directly from renewable feedstocks is rapidly and continually expanding. This of course includes a number of monomer building-block chemicals that can be used to produce replacements to many conventional plastic materials. This review aims to highlight numerous recent and important advancements in the microbial production of these so-called "biomonomers." Relative to naturally-occurring renewable bioplastics, biomonomers offer several important advantages, including improved control over the final polymer structure and purity, the ability to synthesize non-natural copolymers, and allowing products to be excreted from cells which ultimately streamlines downstream recovery and purification. To highlight these features, a handful of biomonomers have been selected as illustrative examples of recent works, including polyamide monomers, styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their industrial penetration to date and end-product uses are also highlighted. Novel biomonomers such as these are ultimately paving the way toward new classes of renewable bioplastics that possess a broader diversity of properties than ever before possible.

Keywords: bioplastics; biopolymers; metabolic engineering; monomers.

Figure 1

The alternative production of “drop in compatible” monomer compounds from biomass feedstocks enables the development of new classes of bio-derived polymers by coupling emerging biotechnologies with mature polymer processing technologies.

Figure 2

Numerous biomonomers can now be produced as a result of metabolic and pathway engineering; examples discussed in this review are depicted here. “Boxed” names signify molecules that have been produced directly from renewable resources, whereas others have been produced via a hybrid, biocatalytic-chemocatalytic approach.

Figure 3

Examples of polyamides (PAs) produced from combinations of C4–C6 diamines, diacids, and amino acids. To date, molecules with names underlined have been produced microbially from renewable resources with the aid of metabolic engineering.

Figure 4

Engineering cadaverine production in Corynebacterium glutamicum by (1) over-expressing L-lysine decarboxylase (cadA), (2) disrupting L-lysine the exporter (lysE), and (3) over-expressing an identified cadaverine exporter (cg2893).

Figure 5

Novel pathways engineered for the production of p-hydroxystyrene and styrene from renewable glucose via aromatic amino acid precursors.

Figure 6

Pathways engineered for stereoselective production of (R)- and (S)-3-hydroxybutyrate and (R)- and (S)-3-hydroxyvalerate from glucose.

Figure 7

Pathway engineered by Yim et al. for the microbial production of 1,4-butanediol (1,4-BDO) through the hydroxyacid intermediate 4-hydroxybutyrate (4HB). 1. 2-oxoglutarate decarboxylase; 2. succinyl-CoA synthetase; 3. CoA-dependent succinate semialdehyde dehydrogenase; 4. 4-hydroxybutyrate dehydrogenase; 5. 4-hydroxybutyryl-CoA transferase; 6. 4-hydroxybutyryl-CoA reductase; 7. alcohol dehydrogenase.