PMID- 23806124
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20220408
IS  - 1475-2859 (Electronic)
IS  - 1475-2859 (Linking)
VI  - 12
DP  - 2013 Jun 28
TI  - Production of hydroxycinnamoyl anthranilates from glucose in Escherichia coli.
PG  - 62
LID - 10.1186/1475-2859-12-62 [doi]
AB  - BACKGROUND: Oats contain hydroxycinnamoyl anthranilates, also named 
      avenanthramides (Avn), which have beneficial health properties because of their 
      antioxidant, anti-inflammatory, and antiproliferative effects. The microbial 
      production of hydroxycinnamoyl anthranilates is an eco-friendly alternative to 
      chemical synthesis or purification from plant sources. We recently demonstrated 
      in yeast (Saccharomyces cerevisiae) that coexpression of 4-coumarate: CoA ligase 
      (4CL) from Arabidopsis thaliana and hydroxycinnamoyl/benzoyl-CoA/anthranilate 
      N-hydroxycinnamoyl/benzoyltransferase (HCBT) from Dianthus caryophyllusenabled 
      the biological production of several cinnamoyl anthranilates upon feeding with 
      anthranilate and various cinnamates. Using engineering strategies to overproduce 
      anthranilate and hydroxycinnamates, we describe here an entire pathway for the 
      microbial synthesis of two Avns from glucose in Escherichia coli. RESULTS: We 
      first showed that coexpression of HCBT and Nt4CL1 from tobacco in the E. coli 
      anthranilate-accumulating strain W3110 trpD9923 allowed the production of Avn D 
      [N-(4'-hydroxycinnamoyl)-anthranilic acid] and Avn F 
      [N-(3',4'-dihydroxycinnamoyl)-anthranilic acid] upon feeding with p-coumarate and 
      caffeate, respectively. Moreover, additional expression in this strain of a 
      tyrosine ammonia-lyase from Rhodotorula glutinis (RgTAL) led to the conversion of 
      endogenous tyrosine into p-coumarate and resulted in the production of Avn D from 
      glucose. Second, a 135-fold improvement in Avn D titer was achieved by boosting 
      tyrosine production using two plasmids that express the eleven genes necessary 
      for tyrosine synthesis from erythrose 4-phosphate and phosphoenolpyruvate. 
      Finally, expression of either the p-coumarate 3-hydroxylase Sam5 from 
      Saccharothrix espanensis or the hydroxylase complex HpaBC from E. coli resulted 
      in the endogenous production of caffeate and biosynthesis of Avn F. CONCLUSION: 
      We established a biosynthetic pathway for the microbial production of valuable 
      hydroxycinnamoyl anthranilates from an inexpensive carbon source. The proposed 
      pathway will serve as a platform for further engineering toward economical and 
      sustainable bioproduction of these pharmaceuticals and other related aromatic 
      compounds.
FAU - Eudes, Aymerick
AU  - Eudes A
AD  - Joint BioEnergy Institute, Emeryville, CA 94608, USA.
FAU - Juminaga, Darmawi
AU  - Juminaga D
FAU - Baidoo, Edward E K
AU  - Baidoo EE
FAU - Collins, F William
AU  - Collins FW
FAU - Keasling, Jay D
AU  - Keasling JD
FAU - Loque, Dominique
AU  - Loque D
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130628
PL  - England
TA  - Microb Cell Fact
JT  - Microbial cell factories
JID - 101139812
RN  - 0 (Caffeic Acids)
RN  - 0 (Fungal Proteins)
RN  - 0 (Plant Proteins)
RN  - 0 (ortho-Aminobenzoates)
RN  - 42HK56048U (Tyrosine)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.14.9 (4-hydroxyphenylacetate 3-monooxygenase)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (anthranilate N-hydroxycinnamoyl benzoyltransferase)
RN  - EC 4.3.1.- (Ammonia-Lyases)
RN  - EC 4.3.1.- (L-tyrosine ammonia-lyase)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.12 (4-coumarate-CoA ligase)
RN  - IY9XDZ35W2 (Glucose)
RN  - U2S3A33KVM (caffeic acid)
SB  - IM
EIN - Microb Cell Fact. 2014;13:8
MH  - Acyltransferases/genetics/metabolism
MH  - Ammonia-Lyases/genetics/metabolism
MH  - Arabidopsis/enzymology
MH  - Biosynthetic Pathways
MH  - Caffeic Acids/metabolism
MH  - Coenzyme A Ligases/genetics/metabolism
MH  - Dianthus/enzymology
MH  - Escherichia coli/*metabolism
MH  - Fungal Proteins/genetics/metabolism
MH  - Genetic Engineering
MH  - Glucose/*metabolism
MH  - Mixed Function Oxygenases/genetics/metabolism
MH  - Plant Proteins/genetics/metabolism
MH  - Plasmids/genetics/metabolism
MH  - Rhodotorula/enzymology
MH  - Tyrosine/biosynthesis
MH  - ortho-Aminobenzoates/*metabolism
PMC - PMC3716870
EDAT- 2013/06/29 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/06/28
CRDT- 2013/06/29 06:00
PHST- 2013/05/25 00:00 [received]
PHST- 2013/06/18 00:00 [accepted]
PHST- 2013/06/29 06:00 [entrez]
PHST- 2013/06/29 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/06/28 00:00 [pmc-release]
AID - 1475-2859-12-62 [pii]
AID - 10.1186/1475-2859-12-62 [doi]
PST - epublish
SO  - Microb Cell Fact. 2013 Jun 28;12:62. doi: 10.1186/1475-2859-12-62.