Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis

Abstract

The biosynthesis of metabolites from available starting materials is becoming an ever important area due to the increasing demands within the life science research area. Access to metabolites is making essential contributions to analytical, diagnostic, therapeutic and different industrial applications. These molecules can be synthesized by the enzymes of biological systems under sustainable process conditions. The facile synthetic access to the metabolite and metabolite-like molecular space is of fundamental importance. The increasing knowledge within molecular biology, enzyme discovery and production together with their biochemical and structural properties offers excellent opportunities for using modular cell-free biocatalytic systems. This reduces the complexity of synthesizing metabolites using biological whole-cell approaches or by classical chemical synthesis. A systems biocatalysis approach can provide a wealth of optimized enzymes for the biosynthesis of already identified and new metabolite molecules.

Advances in the Synthesis and Analysis of Biologically Active Phosphometabolites

“…The synthesis of phosphometabolites has progressed very well and numerous phosphometabolites have become accessible in pure form for the first time. Nevertheless, there is much more work ahead for developing scalable syntheses of known and novel phosphometabolites, reducing the complexity of synthetic routes [ 149 ], improving the molecular economy, and enabling sustainable phosphorus chemistry [ 150 ].…”

Synthesis of Metabolites and Metabolite-like Compounds Using Biocatalytic Systems

“…Biocatalytic whole-cell systems are also connected with a high degree of complexity, which can be reduced by using cell-free biocatalytic systems (see Figure 2) in different forms of purification, from crude cell-free extracts to isolated and purified enzymes. Whatever biocatalytic system is considered, bioprocess design and engineering need to address and optimize various parameters such as biocatalytic pathway selection, form and status of the biocatalysts, reaction engineering, downstream processing, and purification of the metabolites [35,54]. Cell-free biocatalytic systems have the advantage of reducing the bioprocess complexity through the absence of interfering and degrading enzymes or the removal of mass-transfer limitations for substrates and products [54].…”

“…Whatever biocatalytic system is considered, bioprocess design and engineering need to address and optimize various parameters such as biocatalytic pathway selection, form and status of the biocatalysts, reaction engineering, downstream processing, and purification of the metabolites [35,54]. Cell-free biocatalytic systems have the advantage of reducing the bioprocess complexity through the absence of interfering and degrading enzymes or the removal of mass-transfer limitations for substrates and products [54].…”

“…Whatever biocatalytic system is considered, bioprocess design and engineering need to address and optimize various parameters such as biocatalytic pathway selection, form and status of the biocatalysts, reaction engineering, downstream processing, and purification of the metabolites [35,54]. Cell-free biocatalytic systems have the advantage of reducing the bioprocess complexity through the absence of interfering and degrading enzymes or the removal of mass-transfer limitations for substrates and products [54]. While the step economy of a biosynthetic pathway is already considered in the design phase, possible improvements such as complexity reduction, intermediate purification steps, and the number of separate reactors needed are also taken into account by the degree of process integration involved in biocatalytic metabolite synthesis.…”

Synthesis of Metabolites and Metabolite-Like Compounds Using Biocatalytic Systems

“…Biocatalytic whole cell systems are also connected with a high degree of complexity, which can be reduced by using cell-free biocatalytic systems (see Figure 2) in different forms of purification, from crude cell-free extracts to isolated and purified enzymes. Whatever biocatalytic system is considered, bioprocess design and engineering need to address and optimize various parameters such as biocatalytic pathway selection, form and status of the biocatalysts, reaction engineering, downstream processing and purification of the metabolites [34,49]. Cell-free biocatalytic systems have the advantage of reducing the bioprocess complexity by the absence of interfering and degrading enzymes or the removal of mass-transfer limitations for substrates and products [49].…”