Resin acid conversion with CYP105A1: an enzyme with potential for the production of pharmaceutically relevant diterpenoids.
Cytochrome P450s are very versatile enzymes with great potential for biotechnological applications because of their ability to oxidize unactivated CH bonds. CYP105A1 from Streptomyces griseolus was first described as a herbicide-inducible sulfonylurea hydroxylase, but it is also able to convert other substrates such as vitamin D(3) . To extend the substrate pool of this interesting enzyme further, we screened a small diterpenoid compound library and were able to show the conversion of several resin acids. Binding of abietic acid, dehydroabietic acid, and isopimaric acid to the active site was assayed, and V(max)  and K(m)  values were calculated. The products were analyzed by NMR spectroscopy and identified as 15-hydroxyabietic acid, 15-hydroxydehydroabietic acid, and 15,16-epoxyisopimaric acid. As the observed products are difficult to obtain by chemical synthesis, CYP105A1 has proved to be a promising candidate for biotechnological applications that combine bioconversion and chemical synthesis to obtain functionalized resin acids.
Universität des Saarlandes, Biochemie, Campus B2.2, 66123 Saarbrücken, Germany.
Simon
S
Janocha
Josef
J
Zapp
Michael
M
Hutter
Michael
M
Kleser
Jörg
J
Bohlmann
Rita
R
Bernhardt
D045784:Abietanes / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism*; D007218:Industrial Microbiology; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D013305:Streptomyces griseus / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
D045784:Abietanes; D001426:Bacterial Proteins; D004224:Diterpenes; D003577:Cytochrome P-450 Enzyme System; C086254:P450SU1 protein, Streptomyces griseolus; C023710:abietic acid