Synlett 2015; 26(08): 1008-1025
DOI: 10.1055/s-0034-1380264
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© Georg Thieme Verlag Stuttgart · New York

In Vitro Reconstitution of Metabolic Pathways: Insights into Nature’s Chemical Logic

Brian Lowry
a  Department of Chemical Engineering, Stanford University, 443 Via Ortega, Stanford, CA 94305, USA   Email: blowry@stanford.edu
,
Christopher T. Walsh
b  Stanford University Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, 443 Via Ortega, Stanford, CA 94305, USA
,
Chaitan Khosla*
a  Department of Chemical Engineering, Stanford University, 443 Via Ortega, Stanford, CA 94305, USA   Email: blowry@stanford.edu
b  Stanford University Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, 443 Via Ortega, Stanford, CA 94305, USA
c  Department of Chemistry, Stanford University, 333 Campus Drive Mudd Building, Stanford, CA 94305, USA   Email: khosla@stanford.edu   Fax: ???
› Author Affiliations
Further Information

Publication History

Received: 28 November 2014

Accepted after revision: 16 January 2015

Publication Date:
05 March 2015 (online)


Abstract

In vitro analysis of metabolic pathways is becoming a powerful method for gaining a deeper understanding of nature’s core biochemical transformations. Through the astounding advances in biotechnology, the purification of the enzymatic components of a given metabolic pathway is becoming a tractable problem; such in vitro studies permit scientists to capture the fine details of the mechanisms, kinetics, and identities of organic products of enzymatic reactions. In this review, we describe eleven metabolic pathways that have been the subject of recently reported in vitro reconstitution studies. In addition, we have selected and analyzed a subset of four case studies within these eleven examples that exemplify the remarkable organic chemistry that occurs within biological systems. These examples serves as tangible reminders that nature’s biochemical routes obey the fundamental principles of organic chemistry, as their chemical mechanisms are reminiscent of those occurring in conventional synthetic organic routes. The illustrations of biosynthetic chemistry presented in this review might inspire the development of biomimetic chemistries involving abiotic chemical techniques.

1 Introduction

2 Bacterial Metabolites

2.1 Fatty Acids

2.2 Farnesene

2.3 O-Polysaccharides

3 Plant Metabolites

3.1 Dhurrin

3.2 Camalexin

4 Polyketides and Nonribosomal Peptides

4.1 Aromatic Polyketides

4.1.1 Actinorhodin-Derived Polyketides

4.1.2 Enterocin

4.2 Fungal Polyketides

4.2.1 Norsolorinic Acid

4.2.2 Dihydromonacolin L

4.3 Assembly Line Polyketides and Nonribosomal Peptides

4.3.1 6-Deoxyerythronolide B

4.3.2 Asperlicin

5 Discussion of Chemical Insights

5.1 Allylic Carbocation Chemistry Drives Farnesene Synthesis

5.2 Multifunctional Oxidation Chemistry of Cytochrome P450 Enzymes

5.3 A Remarkable Favorskiiase Enzyme Within Enterocin Biosynthesis

5.4 Diels–Alder Chemistry Appears in Biology

6 Concluding Remarks

 
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