Engineering of plant-specific phenylpropanoids biosynthesis in Streptomyces venezuelae.
Phenylpropanoids, including flavonoids and stilbenes, are plant secondary metabolites with potential pharmacological and nutraceutical properties. To expand the applicability of Streptomyces venezuelae as a heterologous host to plant polyketide production, flavonoid and stilbene biosynthetic genes were expressed in an engineered strain of S. venezuelae DHS2001 bearing a deletion of native pikromycin polyketide synthase gene. A plasmid expressing the 4-coumarate/cinnamate:coenzyme A ligase from Streptomyces coelicolor (ScCCL) and the chalcone synthase from Arabidopsis thaliana (atCHS) under the control of a single ermE* promoter was constructed and introduced into S. venezuelae DHS2001. The resulting strain produced racemic naringenin and pinocembrin from 4-coumaric acid and cinnamic acid, respectively. Placement of an additional ermE* promoter upstream of the codon-optimized atCHS (atCHS(op)) gene significantly increased the yield of both flavanones. Expression of codon-optimized chalcone isomerase gene from Medicago sativa, together with ScCCL and atCHS(op) genes led to production of (2S)-flavanones, but the yield was reduced. On the other hand, a recombinant strain harboring the ScCCL and codon-optimized stilbene synthase gene from Arachis hypogaea generated stilbenes such as resveratrol and pinosylvin. This is the first report on the heterologous expression of plant phenylpropanoid biosynthetic pathways in Streptomyces genus.
Park
Sung Ryeol
SR
Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea.
Yoon
Jin A
JA
Paik
Ji Hye
JH
Park
Je Won
JW
Jung
Won Seok
WS
Ban
Yeon-Hee
YH
Kim
Eun Ji
EJ
Yoo
Young Ji
YJ
Han
Ah Reum
AR
Yoon
Yeo Joon
YJ
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D017360:Arabidopsis / Q000201:enzymology*; D003062:Codon; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D044950:Flavanones / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology*
D003062:Codon; D044950:Flavanones; D010940:Plant Proteins; D011994:Recombinant Proteins; D013267:Stilbenes; D000217:Acyltransferases; C020141:flavanone synthetase; D003066:Coenzyme A Ligases