Journal Article

Efficient Mining of Anticancer Peptides from Gut Metagenome

Ma, Yue, Song, Moshi, Zhang, Xuan, Liu, Xiaolin, Li, Yujing, Yu, Ying, Wang, Jun

2023

Overview

The gut microbiome plays a crucial role in modulating host health and disease. It serves as a vast reservoir of functional molecules that hold great potential for clinical applications. One specific area of interest is identifying anticancer peptides (ACPs) for innovative cancer therapies. However, ACPs discovery is hindered by a heavy reliance on experimental methodologies. To overcome this limitation, we here employed a novel approach by leveraging the overlap between ACPs and antimicrobial peptides (AMPs). By combining well‐established AMP prediction methods with mining techniques in metagenomic cohorts, a total of 40 potential ACPs is identified. Out of the identified ACPs, 39 demonstrated inhibitory effects against at least one cancer cell line, exhibiting significant differences from known ACPs. Moreover, the therapeutic potential of the two most promising peptides in a mouse xenograft cancer model is evaluated. Encouragingly, the peptides exhibit effective tumor inhibition without any detectable toxic effects. Interestingly, both peptides display uncommon secondary structures, highlighting its distinctive characteristics. This findings highlight the efficacy of the multi‐center mining approach, which effectively uncovers novel ACPs from the gut microbiome. This approach has significant implications for expanding treatment options not only for CRC, but also for other cancer types. A workflow of discovering anticancer peptides (ACPs) from gut microbiome is devised, combining deeplearning based functional peptides identification and differential analysis in metagenomic data of colorectal cancer patients versus healthy. A total of 39 ACPs is found. The two most potent candidates are safe toward normal cells, with no acute toxicity or significantly reduced tumor growthin animals.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Amino acids / Animals / anticancer peptides / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Cancer / cancer therapy / Cell Line / Data analysis / Datasets / Deep learning / FDA approval / gut microbiome / Humans / Metagenome / Mice / Microbiota / multi‐center mining / Neoplasms - therapy / Peptides / Peptides - chemistry / tumour inhibitors