Abstract:
:Prenylated aromatic compounds are important intermediates in the biosynthesis of bioactive molecules such as 3-chromanols from plants, ubiquinones from prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic compounds using prokaryotic microorganisms has attracted increasing attention in the field of synthetic biology. In this study, we demonstrated that the production of 3-geranyl-4-hydroxybenzoic acid (GBA) and a variety of GBA analogues was feasible in a metabolically engineered E. coli by using XimB, a special prenyltransferase involved in the biosynthesis of xiamenmycin A in Streptomyces xiamenensis 318. XimB exhibits broad substrate specificity and can catalyze the transfer reaction of prenyl moieties with different carbon chain lengths to both the natural substrate 4-hydroxybenzoate (4-HBA) and to different substituted 4-HBA derivatives at C-2 and C-3. Feeding 4-HBA to an engineered E. coli equipped with a hybrid mevalonate pathway increased the production of GBA up to 94.30 mg/L. Considerable amounts of other GBA derivatives, compounds 4, 5, 6, 7, and 9, can be achieved by feeding precursors. The plug-and-play design for inserting C5, C15, and C20 prenyl diphosphate synthetases under the control of the T7 promoter resulted in targeted production of 3-dimethylallyl, 3-farnesyl-, and 3-geranylgeranyl-4-hydroxybenzoic acid, respectively. Furthermore, the valuable benzopyran xiamenmycin B was successfully produced in E. coli R7-MVA by coexpression of a complete biosynthetic gene cluster, which contains ximBDE.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
He BB,Bu XL,Zhou T,Li SM,Xu MJ,Xu Jdoi
10.1021/acssynbio.8b00070subject
Has Abstractpub_date
2018-09-21 00:00:00pages
2094-2104issue
9issn
2161-5063journal_volume
7pub_type
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