title: Metabolic engineering of the L-phenylalanine pathway in Escherichia coli for the production of S- or R-mandelic acid.
abstract: BACKGROUND
  Mandelic acid (MA), an important component in pharmaceutical syntheses, is currently produced exclusively via petrochemical processes. Growing concerns over the environment and fossil energy costs have inspired a quest to develop alternative routes to MA using renewable resources. Herein we report the first direct route to optically pure MA from glucose via genetic modification of the L-phenylalanine pathway in E. coli.
  
  
  RESULTS
  The introduction of hydroxymandelate synthase (HmaS) from Amycolatopsis orientalis into E. coli led to a yield of 0.092 g/L S-MA. By combined deletion of competing pathways, further optimization of S-MA production was achieved, and the yield reached 0.74 g/L within 24 h. To produce R-MA, hydroxymandelate oxidase (Hmo) from Streptomyces coelicolor and D-mandelate dehydrogenase (DMD) from Rhodotorula graminis were co-expressed in an S-MA-producing strain, and the resulting strain was capable of producing 0.68 g/L R-MA. Finally, phenylpyruvate feeding experiments suggest that HmaS is a potential bottleneck to further improvement in yields.
  
  
  CONCLUSIONS
  We have constructed E. coli strains that successfully accomplished the production of S- and R-MA directly from glucose. Our work provides the first example of the completely fermentative production of S- and R-MA from renewable feedstock.
authors.affiliation: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhoutong
authors.initials: Z
authors.lastname: Sun
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ning
authors.forename: Lixia
authors.initials: L
authors.lastname: Liu
authors.forename: Yingmiao
authors.initials: Y
authors.lastname: Liu
authors.forename: Bingbing
authors.initials: B
authors.lastname: Sun
authors.forename: Weihong
authors.initials: W
authors.lastname: Jiang
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
mesh_terms: D053898:Biosynthetic Pathways; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D007536:Isomerism; D008333:Mandelic Acids / Q000737:chemistry / Q000378:metabolism*; D060847:Metabolic Engineering; D010649:Phenylalanine / Q000096:biosynthesis*
chemical_list: D029968:Escherichia coli Proteins; D008333:Mandelic Acids; D010649:Phenylalanine; C037938:mandelic acid