Translating advances in microbial bioproduction to sustainable biotechnology

Abstract

Advances in synthetic biology have radically changed our ability to rewire microorganisms and significantly improved the scalable production of a vast array of drop-in biopolymers and biofuels. The success of a drop-in bioproduct is contingent on market competition with petrochemical analogues and weighted upon relative economic and environmental metrics. While the quantification of comparative trade-offs is critical for accurate process-level decision making, the translation of industrial ecology to synthetic biology is often ambiguous and assessment accuracy has proven challenging. In this review, we explore strategies for evaluating industrial biotechnology through life cycle and techno-economic assessment, then contextualize how recent developments in synthetic biology have improved process viability by expanding feedstock availability and the productivity of microbes. By juxtaposing biological and industrial constraints, we highlight major obstacles between the disparate disciplines that hinder accurate process evaluation. The convergence of these disciplines is crucial in shifting towards carbon neutrality and a circular bioeconomy.

Keywords: bioeconomy; bioproduction; life cycle assessment (LCA); synthetic biology; techno-economic assessment (TEA).

FIGURE 1

The integration of LCA and synthetic biology within a circular bioeconomy. Here, the LCA framework is subdivided into the cradle-to-grave stages of raw material acquisition (feedstocks and pretreatment), manufacturing (DBTL, extraction, and conversion), distribution, use-phase, and end-of-life. For bioproduction platforms, extraction may be further subdivided into bioseparation and media recycling with co-product allocation also accounting for biological waste treatment. Synthetic biology is represented by the DBTL cycle and integrated into the core manufacturing stage of the LCA. The framework enables iterative benchmarking for scaling bioproduction according toTRL.

FIGURE 2

A simplified diagram of feedstock assimilation into bioproduction pathways with specific attention to C1 (CO₂, CO, CH₄, methanol, and formate) as well as lignocellulosic biomass. Pathways are not exhaustive nor necessarily the most efficient, but representative to the selection of bioproducts reviewed. Many other routes have been successfully demonstrated. For example, adipic acid production is depicted from p-coumaric acid via the shikimate pathway and from lignin derivatives, though may be generated from glucaric acid, TCA intermediates, and the β-oxidation pathway. Lignin is represented by a single aromatic, p-coumaric acid, and cis,cis-muconic acid is usually chemically hydrogenated to adipic acid. Likewise, certain pathways have been simplified for clarity (e.g., lysine and CO assimilation). 3-HP acid, 3-hydroxypropionic acid; 6PG, 6-phosphogluconate; CoA, coenzyme A; CODH, carbon monoxide dehydrogenase; DHAP, dihydroxyacetone phosphate; DMAPP, dimethylallyl diphosphate; E4P, erythrose-4-phosphate; F6P, fructose 6-phosphate; FBP, fructose 1,6-bisphosphatase; G3P, glyceraldehyde-3-phosphate; G6P, glucose-6-phosphate; IPP, isopentenyl diphosphate; MEP, methylerythritol 4-phosphate; MVA, mevalonate; OAA, oxaloacetate; PCA, p-coumaric acid; PEP, phosphoenolpyruvate; PHB, poly-3-hydroxybutyrate; R5P, ribose 5-phosphate; rGly, reductive glycine pathway; Ru5P, ribulose 5-phosphate; S7P, sedoheptulose-7-phosphate; Serine, serine cycle; TCA, tricarboxylic acid cycle; VFA, volatile fatty acids; WCO, waste cooking oil Xu5P, xylulose 5-phosphate.