Constructing De Novo Biosynthetic Pathways for Chemical Synthesis Inside Living Cells

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2011 May 20

PMID 21591680

Citations 12

Authors

Amy M Weeks

Michelle C Y Chang

Affiliations

Soon will be listed here.

Abstract

Living organisms have evolved a vast array of catalytic functions that make them ideally suited for the production of medicinally and industrially relevant small-molecule targets. Indeed, native metabolic pathways in microbial hosts have long been exploited and optimized for the scalable production of both fine and commodity chemicals. Our increasing capacity for DNA sequencing and synthesis has revealed the molecular basis for the biosynthesis of a variety of complex and useful metabolites and allows the de novo construction of novel metabolic pathways for the production of new and exotic molecular targets in genetically tractable microbes. However, the development of commercially viable processes for these engineered pathways is currently limited by our ability to quickly identify or engineer enzymes with the correct reaction and substrate selectivity as well as the speed by which metabolic bottlenecks can be determined and corrected. Efforts to understand the relationship among sequence, structure, and function in the basic biochemical sciences can advance these goals for synthetic biology applications while also serving as an experimental platform for elucidating the in vivo specificity and function of enzymes and reconstituting complex biochemical traits for study in a living model organism. Furthermore, the continuing discovery of natural mechanisms for the regulation of metabolic pathways has revealed new principles for the design of high-flux pathways with minimized metabolic burden and has inspired the development of new tools and approaches to engineering synthetic pathways in microbial hosts for chemical production.

Citing Articles

Using Chemical Knowledge to Uncover New Biological Function: Discovery of the Cylindrocyclophane Biosynthetic Pathway.

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Metabolic engineering of for the stereospecific biosynthesis of 1,2-propanediol through lactic acid.

Niu W, Kramer L, Mueller J, Liu K, Guo J Metab Eng Commun. 2018; 8:e00082.

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High-throughput sequencing and de novo transcriptome assembly of Swertia japonica to identify genes involved in the biosynthesis of therapeutic metabolites.

Rai A, Nakamura M, Takahashi H, Suzuki H, Saito K, Yamazaki M Plant Cell Rep. 2016; 35(10):2091-111.

PMID: 27378356 DOI: 10.1007/s00299-016-2021-z.

A highly selective biosynthetic pathway to non-natural C50 carotenoids assembled from moderately selective enzymes.

Furubayashi M, Ikezumi M, Takaichi S, Maoka T, Hemmi H, Ogawa T Nat Commun. 2015; 6:7534.

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Cytochrome P450 Enzyme Metabolites in Lead Discovery and Development.

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