Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.

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Biocatalysis: Enzymatic Synthesis for Industrial Applications

The transition from a fossil fuel-based economy to a bio-based economy necessitates the exploitation of synergies, scientific innovations and breakthroughs, and step changes in the infrastructure of chemical industry. Sustainable production of chemicals and biopolymers should be dependent entirely on renewable carbon. White biotechnology could provide the necessary tools for the evolution of microbial bioconversion into a key unit operation in future biorefineries. Waste and by-product streams from existing industrial sectors (e.g., food industry, pulp and paper industry, biodiesel and bioethanol production) could be used as renewable resources for both biorefinery development and production of nutrient-complete fermentation feedstocks. This review focuses on the potential of utilizing waste and by-product streams from current industrial activities for the production of chemicals and biopolymers via microbial bioconversion. The first part of this review presents the current status and prospects on fermentative production of important platform chemicals (i.e., selected C2-C6 metabolic products and single cell oil) and biopolymers (i.e., polyhydroxyalkanoates and bacterial cellulose). In the second part, the qualitative and quantitative characteristics of waste and by-product streams from existing industrial sectors are presented. In the third part, the techno-economic aspects of bioconversion processes are critically reviewed. Four case studies showing the potential of case-specific waste and by-product streams for the production of succinic acid and polyhydroxyalkanoates are presented. It is evident that fermentative production of chemicals and biopolymers via refining of waste and by-product streams is a highly important research area with significant prospects for industrial applications.

Valorization of industrial waste and by-product streams via fermentation for the production of chemicals and biopolymers

The quest for sustainable polyesters – insights into the future

https://backend.orbit.dtu.dk/ws/files/160753786/1_s2.0_S1096717618301502_main.pdf

Pseudomonas putida as a functional chassis for industrial biocatalysis: From native biochemistry to trans-metabolism.

Many human cancers originate from defects in the DNA damage response (DDR). Although much is known about this process, it is likely that additional DDR genes remain to be discovered. To identify such genes, we used a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis inCaenorhabditis elegans. Together, these approaches identified 12 worm DDR orthologs and 11 novel DDR genes. One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia. Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases.

Combined functional genomic maps of the C-elegans DNA damage response

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(14)00067-5.pdf

Engineering redox balance through cofactor systems

Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its application, and provide insights as to when, what and how different strategies should be taken. In addition, we hi...

DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals

Engineering microbial membranes to increase stress tolerance of industrial strains.

Metabolic engineering of Torulopsis glabrata for malate production.

Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L−1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve d-xylonate productivity of 7.12 g L−1 h−1 with a titer of 199.44 g L−1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production. Current flux rewiring technologies in metabolic engineering are mainly transcriptional regulation. Here, the authors build two sets of controllable protein units using engineered viral proteases and proteolytic signals, and utilize for increasing titers of shikimate and D-xylonate in E. coli.

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Xiulai Chen

Papers

Engineering redox balance through cofactor systems

DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals

Engineering microbial membranes to increase stress tolerance of industrial strains.

Metabolic engineering of Torulopsis glabrata for malate production.

Programmable biomolecular switches for rewiring flux in Escherichia coli.