title: Generation of two new macrolactones through sequential biotransformation of dihydroresorcylide.
abstract: Biotransformation is an effective method to generate new derivatives from natural products. Combination of various enzymes or whole-cell biocatalysts creates new opportunities for natural product biosynthesis. Dihydroresorcylide (1) is a phytotoxic macrolactone from Acremonium aeae. It was first chlorinated at C-11 by an engineered Escherichia coli BL21-CodonPlus (DE3)-RIL/pJZ54 strain that overexpresses a fungal flavin-dependent halogenase, and subsequently glycosylated at 12-OH by Beauveria bassiana ATCC 7159, giving rise to a novel derivative, 11-chloro-4'-O-methyl-12-O-beta-D-glucosyl-dihydroresorcylide (3). Although 1 can be converted into a new 4'-O-methyl-glucosylated derivative 4 by B. bassiana, this product cannot be further chlorinated by E. coli BL21-CodonPlus (DE3)-RIL/pJZ54 to afford 3. The sequence of these two biotransformation steps was thus restricted and not interchangeable. This sequential biotransformation approach can be applied to other structurally similar natural products to create novel derivatives.
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.forename: Jonathan
authors.initials: J
authors.lastname: Valiente
authors.forename: Jixun
authors.initials: J
authors.lastname: Zhan
mesh_terms: D000164:Acremonium / Q000378:metabolism; D052982:Beauveria / Q000378:metabolism*; D001711:Biotransformation; D018942:Macrolides / Q000378:metabolism*
chemical_list: D018942:Macrolides; C530147:dihydroresorcylide