Allelopathic Polyketides from an Endolichenic Fungus Myxotrichum SP. by Using OSMAC Strategy

Abstract

Three new polyketides myxotritones A-C (2-4), together with a new natural product 7,8-dihydro-7R,8S-dihydroxy-3,7-dimethyl-2-benzopyran-6-one (1) were obtained from the endolichenic fungus Myxotrichum sp. by using OMSAC (One Strain, Many Compounds) method. The planar structures of these new compounds were determined by NMR experiment and HRESIMS data, and the absolute configuration of 1 was established by X-ray diffraction, and the stereochemistry of the new compounds 2-4 were determined by same biosynthesis origin, and similar CD spectra with 1. Allelopathic test showed that compound 4 significantly retarded root elongation of Arabidopsis thaliana seed, indicating that this fungus might contribute to the defense of its host lichen. From the view of biosynthetic pathway, all four compounds 1-4 might be originated from Non-Reduced Polyketide synthase (NR-PKS).Lichens are combinations of a fungus (the mycobiont) and an algal partner (the photobiont or phycobiont). In addition to fungal mycobionts, some nonobligate fungi, such as endolichenic fungi, are also found to live asymptomatically in the bodies (thalli) of lichens 1 . Although endolichenic fungi inhabit the lichen thalli similarly to endophytes living in the intercellular spaces of healthy plant tissues, the chemistry of this class of fungi remained largely unexplored 2 . Analysis of a great number genome sequence from different microbes revealed that many secondary metabolite biosynthetic gene clusters are silent under common cultivation conditions, and their metabolic potentials were underestimated. To activate the cryptic gene cluster to express, different methods were innovated 3 . One easiest way is to vary the culture media to induce different cryptic gene cluster to express and then obtain new/novel secondary metabolites. This approach was termed as "One Strain, Many Compounds" first suggested by Germany natural product chemist Prof. A Zeek 4 . In our previous report, a series of citromycetin and fulvic acid with unique skeletons have been obtained from the PDB culture of endolichenic fungus Myxotrichum sp 5 (Fig. 1). To dig the metabolic potential of endolichenic fungi Myxotrichum sp., rice culture was used to activate the potentially silent gene clusters, from which three new polyketides myxotritones A-C (2-4), together with a new natural product 7, 8-dihydro-7R, 8S-dihydroxy-3, 7-dimethyl-2-benzopyran-6-one (1) were obtained. In this report, the structural elucidation, biological evaluation, and possible biosynthetic pathway were present. Results and DiscussionThe known compound 1 is identified to be as 7, 8-dihydro-7R, 8S-dihydroxy-3, 7-dimethyl-2-benzopyran-6-one based on the NMR, MS data and optical rotation [α ] D 22 = + 393.0 (c = 0.15, MeOH), which was known as a synthetic compound but never isolated from a natural specimen 6,7 (Fig. 2). Fortunately, a suitable crystal was obtained for X-ray diffraction (in MeOH) (Fig. S5). The planar structure and absolute configuration of 1 were confirmed by single-crystal X-ray diffraction analysis with C...

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