Abstract
Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.
Highlights
Nature’s strength and beauty come from its diversity in biochemical systems, which generate and degrade essential and non-essential chemical substances in living single cells or multicellular organisms through different biochemical reactions that collectively form cellular metabolism
We aim to provide current insights and future perspectives on how progress in the state-of-the-art approaches in metabolic pathway diversification for the production of novel value-added compounds will eventually facilitate the development of efficient designer microorganisms that can potentially meet most of the chemical needs of modern civilization
Synthesis of optically pure D-lactic acid was achieved in E. coli by expression of engineered glycerol dehydrogenase evolved for D-lactate dehydrogenase activity
Summary
Nature’s strength and beauty come from its diversity in biochemical systems, which generate and degrade essential and non-essential chemical substances in living single cells or multicellular organisms through different biochemical reactions (i.e., metabolic pathways) that collectively form cellular metabolism. A diverse range of biochemicals are present in nature Many of these biochemicals are secondary metabolites to the native organisms but are of high biotechnological value to industries (Oksman-Caldentey and Inze, 2004; Harvey, 2008; Dhakal et al, 2017). Characterization of these secondary metabolites and exploration of the metabolic networks involved can potentially enable sustainable production of valuable. We aim to provide current insights and future perspectives on how progress in the state-of-the-art approaches in metabolic pathway diversification for the production of novel value-added compounds will eventually facilitate the development of efficient designer microorganisms that can potentially meet most of the chemical needs of modern civilization. We will review efforts in production of value-added compounds accomplished through rewriting of metabolic network with natural and non-natural enzymes, as well as computational design of non-natural metabolic pathways
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