title: Production of phenylacetyl-homoserine lactone analogs by artificial biosynthetic pathway in Escherichia coli.
abstract: BACKGROUND
  Quorum sensing (QS) networks are more commonly known as acyl homoserine lactone (HSL) networks. Recently, p-coumaroyl-HSL has been found in a photosynthetic bacterium. p-coumaroyl-HSL is derived from a lignin monomer, p-coumaric acid, rather than a fatty acyl group. The p-coumaroyl-HSL may serve an ecological role in diverse QS pathways between p-coumaroyl-HSL producing bacteria and specific plants. Interference with QS has been regarded as a novel way to control bacterial infections. Heterologous production of the QS molecule, p-coumaroyl-HSL, could provide a sustainable and controlled means for its large-scale production, in contrast to the restricted feedback regulation and extremely low productivity of natural producers.
  
  
  RESULTS
  We developed an artificial biosynthetic process for phenylacetyl-homoserine lactone analogs, including cinnamoyl-HSL, p-coumaroyl-HSL, caffeoyl-HSL, and feruloyl-HSL, using a bioconversion method via E. coli (CB1) in the co-expression of the codon-optimized LuxI-type synthase (RpaI) and p-coumaroyl-CoA ligase (4CL2nt). In addition to this, we show the de novo production of p-coumaroyl-HSL in heterologous host E. coli (DN1) and tyrosine overproducing E. coli (DN2), containing the rpaI gene in addition to p-coumaroyl-CoA biosynthetic genes. The yields for p-coumaroyl-HSL reached 93.4 ± 0.6 and 142.5 ± 1.0 mg/L in the S-adenosyl-L-methionine and L-methionine feeding culture in the DN2 strain, respectively.
  
  
  CONCLUSIONS
  This is the first report of a de novo biosynthesis in a heterologous host yielding a QS molecule, p-coumaroyl-HSL from a glucose medium using a single vector system combining p-coumaroyl-CoA biosynthetic genes and the LuxI-type synthase gene.
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Chungbuk, 363-883, Republic of Korea. kangsun111@kribb.re.kr.|Department of Pharmacy Graduate School, Chungbuk National University, Cheongju, 361-763, Republic of Korea. kangsun111@kribb.re.kr.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Chungbuk, 363-883, Republic of Korea. scarscar@kribb.re.kr.|Department of Pharmacy Graduate School, Chungbuk National University, Cheongju, 361-763, Republic of Korea. scarscar@kribb.re.kr.
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Chungbuk, 363-883, Republic of Korea. jangjh@kribb.re.kr.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Pharmacy Graduate School, Chungbuk National University, Cheongju, 361-763, Republic of Korea. byhwang@chungbuk.ac.kr.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Chungbuk, 363-883, Republic of Korea. hongsoo@kribb.re.kr.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing; D014026:Nicotiana / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D010940:Plant Proteins; C088386:homoserine lactone; D014443:Tyrosine; D003066:Coenzyme A Ligases; D015107:4-Butyrolactone