Gene mining and efficient biosynthesis of a fungal peptidyl alkaloid / 中草药·英文版

Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal non-ribosomal peptide synthetases (NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs. Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed. Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out. Results: The putative tri-modular NRPS AncA was heterologous-expressed in A. nidulans to give anacine (1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line. Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.

Hetero-biosynthesis of the main bioactive components from medicinal fungus Shiraia bambusiccola / 药学学报

italic>Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.

Six new monacolin analogs from red yeast rice / 中国天然药物

Six novel monacolin analogs, monacolins V-V (1-6), together with seven known ones (7-13), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods, especially 2D NMR (H-HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation. Monacolins V (2) and V (3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide (LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.