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-β-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.
HollandHL, MorrisTA, NavaPJ, ZabicM. (1999) A new paradigm for biohydroxylation by Beauveria bassiana ATCC 7159. Tetrahedron, 55, 7441-7460.
2.
GroganGJ, HollandHL. (2000) The biocatalytic reactions of Beauveria spp. Journal of Molecular Catalysis B: Enzymatic, 9, 1-32.
3.
ZhanJ, GunatilakaAal. (2005) Microbial transformation of curvularin. Journal of Natural Products, 681271-1273;
4.
ZhanJ, GunatilakaAal. (2006) Selective 4′-O-methylglycosylation of the pentahydroxy-flavonoid quercetin by Beauveria bassiana ATCC 7159. Biocatalysis and Biotransformation, 24396-399;
5.
ZhanJ, GunatilakaAal. (2006) Microbial transformation of amino- and hydroxyanthraquinones by Beauveria bassiana ATCC 7159. Journal of Natural Products, 691525-1527;
6.
ZhanJ, GunatilakaAal. (2008) Microbial metabolism of 1-aminoanthracene by Beauveria bassiana. Bioorganic & Medicinal Chemistry, 165085-5089;
7.
ZengJ, YangN, LiX, ShamiPJ, ZhanJ. (2010) 4′-O-Methylation of curcumin by Beauveria bassiana. Natural Product Communications, 5, 77-80.
8.
ZengJ, ZhanJ. (2010) A novel fungal flavin-dependent halogenase for natural product biosynthesis. ChemBioChem, 112119-2123;
9.
ShinonagaH, KawamuraY, IkedaA, AokiM, SakaiN, FujimotoN, KawashimaA. (2009) Pochonins K-P: new radicicol analogues from Pochonia chlamydosporia var. chlamydosporia and their WNT-5A expression inhibitory activities. Tetrahedron, 653446-3453;
10.
EvansG, WhiteNH. (1966) Radicicolin and radicicol, two new antibiotics produced by Cylindrocarpon radicicola. Transactions of the British Mycological Society, 49563-576;
11.
TurbyvilleTJ, WijeratneEmk, LiuMX, BurnsAM, SeligaCJ, LuevanoLA, DavidCL, FaethSH, WhitesellL, GunatilakaAal. (2006) Search for Hsp90 inhibitors with potential anticancer activity: Isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desert. Journal of Natural Products, 69178-184;
12.
WicklowDT, JordanAM, GloerJB. (2009) Antifungal metabolites (monorden, monocillins I, II, III) from Colletotrichum graminicola, a systemic vascular pathogen of maize. Mycological Research, 113, 1433-1442.
13.
PolingSM, WicklowDT, RogersKD, GloerJB. (2008) Acremonium zeae, a protective endophyte of maize produces dihydroresorcylide and 7-hydroxydihydroresorcylides. Journal of Agricultural and Food Chemistry, 563006-3009;
14.
ZengJ, ValienteJ, ZhanJ. (2010) Specific inhibition of the halogenase for radicicol biosynthesis by bromide at the transcription level in Pochonia chlamydosporia. Biotechnology Letters, 33333-338;
15.
AltreuterDH, ClarkDS. (1999) Combinatorial biocatalysis: taking the lead from Nature. Current Opinion in Biotechnology, 10, 130-136.
16.
HarrisCM, KannanR, KopeckaH, HarrisTM. (1985) The role of the chlorine substituents in the antibiotic vancomycin: preparation and characterization of mono- and didechlorovancomycin Journal of the American Chemical Society, 107, 6652-6658.
