Anguinomycin A

Basal stem rot (BSR), orGanodermarot disease, is the most serious disease associated with the oil palm plant of Southeast Asian countries. A basidiomycetous fungus,Ganoderma boninense, is the causative microbe of this disease. To control BSR in oil palm plantations, biological control agents are gaining attention as a major alternative to chemical fungicides. In the course of searching for effective actinomycetes as potential biological control agents for BSR,Streptomyces palmaeCMU-AB204Twas isolated from oil palm rhizosphere soil collected on the campus of Chiang Mai University. The culture broth of this strain showed significant antimicrobial activities against several bacteria and phytopathogenic fungi includingG. boninense. Antifungal and antibacterial compounds were isolated by antimicrobial activity-guided purification using chromatographic methods. Their structures were elucidated by spectroscopic techniques, including Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), Ultraviolet (UV), and Infrared (IR) analyses. The current study isolated new phenyl alkenoic acids1-6and three known compounds, anguinomycin A (7), leptomycin A (8), and actinopyrone A (9) as antimicrobial agents. Compounds1and2displayed broad antifungal activity, though they did not show antibacterial activity. Compounds3and4revealed a strong antibacterial activity against both Gram-positive and Gram-negative bacteria including the phytopathogenic strainXanthomonas campestrispv.oryzae. Compounds7-9displayed antifungal activity againstGanoderma. Thus, the antifungal compounds obtained in this study may play a role in protecting oil palm plants fromGanodermainfection with the strainS. palmaeCMU-AB204T.

The polyketide natural product Leptomycin B inhibits nuclear export mediated by the karyopherin protein chromosomal region maintenance 1 (CRM1). Here, we present 1.8- to 2.0-Å-resolution crystal structures of CRM1 bound to Leptomycin B and related inhibitors Anguinomycin A and Ratjadone A. Structural and complementary chemical analyses reveal an unexpected mechanism of inhibition involving covalent conjugation and CRM1-mediated hydrolysis of the natural products' lactone rings. Furthermore, mutagenesis reveals the mechanism of hydrolysis by CRM1. The nuclear export signal (NES)-binding groove of CRM1 is able to drive a chemical reaction in addition to binding protein cargoes for transport through the nuclear pore complex.