The future of metabolic engineering and synthetic biology: Towards a systematic practice

Abstract

Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering.

Progress and perspective on lignocellulosic hydrolysate inhibitor tolerance improvement in Zymomonas mobilis

“…Considering that even simple modification in genome may switch cellular metabolism or redox balance and thereby decrease the overall yield of the system, sophisticated computational models should be developed to guide future genetic or metabolic engineering efforts in Z. mobilis (Kalnenieks et al 2014;Widiastuti et al 2011;Yadav et al 2012). In addition, with the rapid development of synthetic biology tools and strategies especially the recent breakthrough on yeast genome synthesis Xie et al 2017;Zhang et al 2017), it is advantageous and practical to develop ZM4 as a chassis microorganism through both genome minimization and genome synthesis approaches considering its excellent industrial features, small genome size of 2.06 Mb, and fascinating unique physiology.…”

New Insight into the Cleavage Reaction of Nostoc sp. Strain PCC 7120 Carotenoid Cleavage Dioxygenase in Natural and Nonnatural Carotenoids

“…Synthetic biological approaches have been widely used for the redesign and reconstruction of biosynthetic pathways in heterologous hosts (18,19). The functional, modular expression of redesigned pathway enzymes can improve the productivity and yield of target molecules (20).…”

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

“…[29] Of the two pathways, the DXP pathway is more energetically balanced and efficient than the MEV pathway. [30] However, in the case of terpenoids production Enzymes that the corresponding genes encode are as follows: dxr, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; dxs, 1-deoxy-D-xylulose 5-phosphate synthase; gapA, glyceraldehyde 3-phosphate dehydrogenase; idi, isopentenyl pyrophosphate isomerase; ispD, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; ispE, 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase; ispF, 4-diphosphocytidyl-2-Cmethyl-D-erythritol kinase; ispG, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase; ispH, 4-hydroxy-3-methylbut-2-enyl diphosphate reductase; pps, phosphoenolpyruvate synthase. Abbreviations can be found in the appendix.…”