Producing mass quantities of chemicals has its roots in the industrial revolution. But industrial synthesis leads to sizeable sustainability and socioeconomic challenges. The rapid advances in biotechnology suggest that biological manufacturing may soon be a feasible alternative, but can it produce chemicals at scale? Clomburg et al. review the progress made in industrial biomanufacturing, including the tradeoffs between highly tunable biocatalysts and units of scale. The biological conversion of single-carbon compounds such as methane, for example, has served as a testbed for more sustainable, decentralized production of desirable compounds.

Science , this issue p. [10.1126/science.aag0804][1]

 [1]: /lookup/doi/10.1126/science.aag0804

http://science.sciencemag.org/content/sci/355/6320/aag0804.full.pdf

Industrial biomanufacturing: The future of chemical production

Renewable methanol and formate as microbial feedstocks

Recent studies of multiple enzyme families collectively called ene-reductases (ERs) have highlighted potential industrial applications of these biocatalysts in the production of fine and specialty chemicals. Processes have been developed whereby ERs contribute to synthetic routes as isolated enzymes, as components of multienzyme cascades, and more recently in metabolic engineering and synthetic biology programs using microbial cell factories to support chemicals production. The discovery of ERs from previously untapped sources and the expansion of directed-evolution screening programs, coupled to deeper mechanistic understanding of ER reactions, have driven their use in natural product and chemicals synthesis. Here we review developments, challenges, and opportunities for the use of ERs in fine and specialty chemicals manufacture. The ER research field is rapidly expanding, and the focus of this review is on developments that have emerged predominantly over the last 4 years.

/pdf/discovery-characterisation-engineering-and-applications-of-2gqrd9syw5.pdf

Discovery, Characterisation, Engineering and Applications of Ene Reductases for Industrial Biocatalysis

Global climate change caused by the accumulation of greenhouse gases (GHGs) has caused concerns regarding the continued reliance on fossil fuels as our primary energy source. Hydrocarbons produced from biomass using microbial fermentation processes can serve as high-quality liquid transportation fuels and may contribute to a reduction in GHG emissions. Here, we discuss the barriers and opportunities for bio-based production of hydrocarbons to be used as diesel and jet fuels and review recent advances in engineering microbes for production of these chemicals. There are two main challenges associated with establishing bio-based hydrocarbon production from cheap feedstocks; lowering the cost of developing efficient and robust microbial cell factories and establishing more efficient routes for biomass hydrolysis to sugars for fermentation. We discuss how to develop novel systems and synthetic biology tools that can enable faster and cheaper construction of microbial cell factories and thereby address the first challenge, as well as recent advances in biomass processing that will likely lead to overcoming the second challenge in the near future.

/pdf/barriers-and-opportunities-in-bio-based-production-of-4hwmf1a9mx.pdf

Barriers and opportunities in bio-based production of hydrocarbons

Terpenoid flavor and fragrance compounds are of high interest to the aroma industry. Microbial production offers an alternative sustainable access to the desired terpenoids independent of natural sources. Genetically engineered microorganisms can be used to synthesize terpenoids from cheap and renewable resources. Due to its modular architecture, terpenoid biosynthesis is especially well suited for the microbial cell factory concept: a platform host engineered for a high flux toward the central C5 prenyl diphosphate precursors enables the production of a broad range of target terpenoids just by varying the pathway modules converting the C5 intermediates to the product of interest. In this review typical terpenoid flavor and fragrance compounds marketed or under development by biotech and aroma companies are given, and the specificities of the aroma market are discussed. The main part of this work focuses on key strategies and recent advances to engineer microbes to become efficient terpenoid producers.

Microbial Cell Factories for the Production of Terpenoid Flavor and Fragrance Compounds

Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid α-humulene from methanol.

Power-to-X technologies have the potential to pave the way towards a future resource-secure bioeconomy as they enable the exploitation of renewable resources and CO2 . Herein, the coupled electrocatalytic and microbial catalysis of the C5 -polymer precursors mesaconate and 2S-methylsuccinate from CO2 and electric energy by in situ coupling electrochemical and microbial catalysis at 1 L-scale was developed. In the first phase, 6.1±2.5 mm formate was produced by electrochemical CO2 reduction. In the second phase, formate served as the substrate for microbial catalysis by an engineered strain of Methylobacterium extorquens AM-1 producing 7±2 μm and 10±5 μm of mesaconate and 2S-methylsuccinate, respectively. The proof of concept showed an overall conversion efficiency of 0.2 % being 0.4 % of the theoretical maximum.

https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cssc.202001272

Coupled Electrochemical and Microbial Catalysis for the Production of Polymer Bricks.

Old yellow enzymes are able to catalyze asymmetric C=C reductions. A mediated electroenzymatic process to regenerate the NADPH in combination with an old yellow enzyme was investigated. Due to the fact that the overall process was affected by a broad set of parameters, a design of experiments (DoE) approach was chosen to identify suitable process conditions. Process conditions with high productivities of up to 2.27 mM/h in combination with approximately 90% electron transfer efficiency were identified.

/pdf/towards-electroenzymatic-processes-involving-old-yellow-47vfk6chkp.pdf

Towards electroenzymatic processes involving old yellow enzymes and mediated cofactor regeneration.

The invention relates to microbial production of terpenes. Known processes of microbial production of terpenes are based mostly on direct conversion of sugars. It was therefore desirable to have alternative substrates, and especially alternative carbon sources, for use in microbial production of terpenes. The invention relates to a methylotrophic bacterium with recombinant DNA encoding at least one polypeptide having enzymatic activity for heterologous expression in the stated bacterium, the said at least one polypeptide having enzymatic activity being selected from the group consisting of an enzyme of a heterologous mevalonate pathway, a heterologous terpene synthase and optionally a heterologous synthase of a prenyl diphosphate precursor. The invention also relates in particular to a process for de novo microbial synthesis of sesquiterpenes or diterpenes from methanol and/or ethanol.

Process for de novo microbial synthesis of terpenes

Climate change and the finite nature of fossil fuels raise the need for the fixation of CO2 and conversion into traditionally petroleum-derived chemicals. With Cupriavidus necator as an easily genetically modifiable biocatalyst, a wide range of products, e. g. polymers, platform chemicals, biofuels, and terpenes, can be accessed. The wide range of applications as well as a prominent example of electrochemical α-humulene production from CO2 are promising developments towards a bio-based society.

Cora Kroner

Papers

Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid α-humulene from methanol.

Coupled Electrochemical and Microbial Catalysis for the Production of Polymer Bricks.

Towards electroenzymatic processes involving old yellow enzymes and mediated cofactor regeneration.

Process for de novo microbial synthesis of terpenes

Knallgasbakterien – neue Synthesewege mit Cupriavidus necator