Three new resorcylic acid derivatives from Sporotrichum laxum

Sporotrichum laxum ATCC 15155 is the producing strain of the potent anti-Helicobacter pylori natural product spirolaxine (1). Investigation of the secondary metabolites in this fungus led to the isolation of five phthalides (1, 2, 3, 6 and 9) and five resorcylic acid derivatives (4, 5, 7, 8 and 10), among which 5, 7 and 8 are new compounds. The structures were elucidated by spectroscopic analyses, and the absolute configurations of 7 and 8 were determined by Mosher's method. Addition of soy flour into the potato dextrose agar has led to the increased production of 4-10. A biosynthetic pathway consisting of a highly reducing polyketide synthase (PKS), a nonreducing PKS and a series of tailoring enzymes was proposed to produce these fungal natural products. The resorcylic acid derivatives are proposed to result from early hydrolysis of the polyketide chain or incorporation of a longer fatty acyl starter unit.