AUTHOR=Wang Xiaohan , Jiang Dan , Shi Qijin , Ren Guangxi , Liu Chunsheng 

TITLE=Microbial degradation of aristolochic acid I by endophytic fungus A.h-Fs-1 of Asarum heterotropoides

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.917117

DOI=10.3389/fmicb.2022.917117

ISSN=1664-302X

ABSTRACT=<p>Asari Radix et Rhizoma is commonly used in classic prescriptions of herbal medicine in several Asian countries for resuscitation, pain relief, and sore treatment, and <italic>Asarum heterotropoides</italic> (<italic>A. heterotropoides</italic>) is an important source material of Asari Radix et Rhizoma. However, the plants of the Asari Radix et Rhizoma and some plants in <italic>Asarum</italic> spp. contain aristolochic acid I (AAI), which is considered as a carcinogen. The objective of the current study is to detoxify <italic>Asarum</italic> spp. through microbial degradation of AAI in order to ensure drug safety. Based on the observation of the close correlation between endophytic fungi of <italic>A. heterotropoides</italic> and AAI, we identified an AAI-degrading fungus and screened for candidate genes involved in AAI degradation. Full-length <italic>O</italic>-demethylase genes (<italic>ODMs</italic>) were cloned including <italic>A.h-ODM-5</italic>, <italic>Fs-ODM-4,</italic> and <italic>Fs-ODM-1</italic>, and their ability to degrade AAI was tested <italic>in vitro</italic>. The results showed that the AAI-degrading fungus was identified as <italic>Neocosmospora solani</italic> (A.h-Fs-1, endophytic fungi of <italic>A. heterotropoides</italic>), and verified the capability of specific <italic>O</italic>-demethylation to modify the structure of AAI. We further identified the functional ODMs in A.h-Fs-1 capable of degrading AAI and uncovered the AAI degradation mechanism of A.h-Fs-1. The microbial degradation of AAI demonstrated in the present study offers a new method to detoxify plant materials used for herbal medicine, and would enhance the regulation of toxic ingredients content in herbal medicine source materials.</p>