Endophytes Are Hidden Producers of Maytansine in Putterlickia Roots

Several recent studies have lent evidence to the fact that certain so-called plant metabolites are actually biosynthesized by associated microorganisms. In this work, we show that the original source organism(s) responsible for the biosynthesis of the important anticancer and cytotoxic compound maytansine is the endophytic bacterial community harbored specifically within the roots of Putterlickia verrucosa and P. retrospinosa plants. Evaluation of the root endophytic community by chemical characterization of their fermentation products using HPLC-HRMSn, along with a selective microbiological assay using the maytansine-sensitive type strain Hamigera avellanea revealed the endophytic production of maytansine. This was further confirmed by the presence of AHBA synthase genes in the root endophytic communities. Finally, MALDI-imaging-HRMS was used to demonstrate that maytansine produced by the endophytes is typically accumulated mainly in the root cortex of both plants. Our study, thus, reveals that maytansine is actually a biosynthetic product of root-associated endophytic microorganisms. The knowledge gained from this study provides fundamental insights on the biosynthesis of so-called plant metabolites by endophytes residing in distinct ecological niches

Endophytic <i>Diaporthe</i> sp. LG23 Produces a Potent Antibacterial Tetracyclic Triterpenoid

A new lanostanoid, 19-nor-lanosta-5(10),6,8,24-tetraene-1α,3β,12β,22<i>S</i>-tetraol (<b>1</b>), characterized by the presence of an aromatic B ring and hydroxylated at C-1, C-3, C-12, and C-22, was isolated from an endophytic fungus, <i>Diaporthe</i> sp. LG23, inhabiting leaves of the Chinese medicinal plant <i>Mahonia fortunei</i>. Six biosynthetically related known steroids were also isolated in parallel. Their structures were confirmed on the basis of detailed spectroscopic analysis in conjunction with the published data. Compound <b>1</b>, an unusual fungus-derived 19-nor-lanostane tetracyclic triterpenoid with an aromatic B-ring system, exhibited pronounced antibacterial efficacy against both Gram-positive and -negative bacteria, especially the clinical isolates of <i>Streptococcus pyogenes</i> and <i>Pseudomonas aeruginosa</i> as well as a human pathogenic strain of <i>Staphylococcus aureus</i>. Our results reveal the potential of endophytes not only in conferring host fitness but also in contributing toward traditional host plant medicines

Antibacterial Azaphilones from an Endophytic Fungus, <i>Colletotrichum</i> sp. BS4

Three new compounds, colletotrichones A–C (<b>1</b>–<b>3</b>), and one known compound, chermesinone B (<b>4a</b>), were isolated from an endophytic fungus, <i>Colletotrichum</i> sp. BS4, harbored in the leaves of <i>Buxus sinica</i>, a well-known boxwood plant used in traditional Chinese medicine (TCM). Their structures were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRMS, ECD spectra, UV, and IR, as well as single-crystal X-ray diffraction, and shown to be azaphilones sharing a 3,6a-dimethyl-9-(2-methylbutanoyl)-9<i>H</i>-furo­[2,3-<i>h</i>]­isochromene-6,8-dione scaffold. Owing to the remarkable antibacterial potency of known azaphilones coupled to the usage of the host plant in TCM, we evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of <i>Escherichia coli</i> and <i>Bacillus subtilis</i>, as well as against two human pathogenic clinical strains of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. Compound <b>1</b> exhibited marked antibacterial potencies against the environmental strains that were comparable to the standard antibiotics. Compound <b>3</b> was also active against <i>E. coli</i>. Finally, compound <b>2a</b> exhibited the same efficacy as streptomycin against the clinically relevant bacterium <i>S. aureus</i>. The <i>in vitro</i> cytotoxicity of these compounds on a human acute monocytic leukemia cell line (THP-1) was also assessed. Our results provide a scientific rationale for further investigations into endophyte-mediated host chemical defense against specialist and generalist pathogens

Endophytes Are Hidden Producers of Maytansine in <i>Putterlickia</i> Roots

Several recent studies have lent evidence to the fact that certain so-called plant metabolites are actually biosynthesized by associated microorganisms. In this work, we show that the original source organism(s) responsible for the biosynthesis of the important anticancer and cytotoxic compound maytansine is the endophytic bacterial community harbored specifically within the roots of <i>Putterlickia verrucosa</i> and <i>P. retrospinosa</i> plants. Evaluation of the root endophytic community by chemical characterization of their fermentation products using HPLC-HRMS^<i>n</i>, along with a selective microbiological assay using the maytansine-sensitive type strain <i>Hamigera avellanea</i> revealed the endophytic production of maytansine. This was further confirmed by the presence of AHBA synthase genes in the root endophytic communities. Finally, MALDI-imaging-HRMS was used to demonstrate that maytansine produced by the endophytes is typically accumulated mainly in the root cortex of both plants. Our study, thus, reveals that maytansine is actually a biosynthetic product of root-associated endophytic microorganisms. The knowledge gained from this study provides fundamental insights on the biosynthesis of so-called plant metabolites by endophytes residing in distinct ecological niches