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Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli
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Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli
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Journal Article
Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli
2016
Overview
Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that
Escherichia coli
serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l
−1
from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (
R
)-reticuline in
E. coli
. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this
E. coli
system represent a major step towards the development of alternative opiate production systems.
Opiates—the gold standard for pain relief—are currently produced by extraction from opium poppies. Here the authors show that bacteria can serve as an efficient and flexible platform for the production of opiates by demonstrating the total synthesis of Thebaine and hydrocodone from stepwise fermentation in
E. coli
.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/22
/ 38/77
/ 82/58
/ 82/80
/ Acetyltransferases - genetics
/ Analgesics, Opioid - metabolism
/ Benzylisoquinolines - metabolism
/ E coli
/ Escherichia coli - metabolism
/ Humanities and Social Sciences
/ Methyltransferases - genetics
/ Methyltransferases - metabolism
/ Organisms, Genetically Modified - genetics
/ Organisms, Genetically Modified - metabolism
/ Science
/ Yeasts
