Skip to content
DraconiticResearch
Search Sources API
190,860 studies31 sourcesUpdated 44 min ago
Peer-reviewedCC BY-NC-NDSynthetic and systems biotechnology

A base-editing and auxotrophic selection platform for linking epigenetic regulators to silent biosynthetic gene clusters in Aspergillus nidulans.

  • Meng Pang1,2
  • Donghui Guo1
  • Yanling Li1
  • Yuze Chen1
  • Rumeng Du1
  • Jiayang Liu1
  • Jiahui Hu1
  • Hang Li1
  • Zhuofan Li1
  • Guojun Pan1,2
  • Yuan Tian1,2,3
  • Fanglong Zhao1,2,3
  1. 1School of Life Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, China.
  2. 2Science and Technology Innovation Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
  3. 3Integrative Centre for Frontier Biotech and Pharmaceutical Sciences, Shandong First Medical University, Taian, Shandong, 271016, China.
Read full textPDFDOICite

Abstract

Filamentous fungi harbor numerous silent biosynthetic gene clusters (BGCs), representing an underexplored reservoir of natural products. Chemical inhibition of epigenetic regulators is an effective strategy for activating silent BGCs, but it often lacks specificity and cannot readily link activated clusters to their cognate regulators. Here, we developed a coupled cytosine base editing and auxotrophic selection platform in Aspergillus nidulans to systematically identify epigenetic regulators of silent gene clusters. An sgRNA library targeting 24 core epigenetic regulators was introduced, together with a cytosine base editor, into 21 pyrG-based PKS reporter strains, enabling growth-based selection and direct sgRNA recovery by Sanger sequencing. This screen identified five regulator-cluster activation pairs, including known interactions and two previously uncharacterized mechanisms. Specifically, KdmB represses the AN7084 gene cluster by erasing promoter H3K4me3, whereas Kmt5 silences the cichorine core pks gene through H4K20me3 deposition. This scalable platform enables rapid matching of silent BGCs with their epigenetic regulators and advances chromatin-guided fungal genome mining.

Related

  1. Antifungal susceptibility and genomic profile associated with biosynthetic gene clusters of bovine mastitis-derived Aspergillus fumigatus DAH1043FM
    Abhishek Prajapati, Pooja Parmar, Monica Chavan +7
    Frontiers in microbiologyPeer-reviewedCC BYFull textInfectious diseaseEurope PMCCrossref
  2. Tertiary structure of a Nif11-like leader peptide mediates protein-protein interactions with a RiPP biosynthetic enzyme
    M. A. Wakeel, F. Vidya, C. E. Merrick +6
    bioRxivPreprintAll rights reservedFull textPharmacology & toxicologybioRxiv
  3. An automated operon refactoring workflow for heterologous expression of non-ribosomal peptide biosynthetic gene clusters
    Zhibo Li, Lifu Liu, Xingyan Sun +15
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full textPharmacology & toxicologyCrossref
  4. Case Report: Analysis of antimicrobial therapy and pharmaceutical care of mixed Aspergillus and Mycobacterium tuberculosis infection following renal transplantation: a case study
    Jiao Zhang, Yue Zhao, Yang Peng +1
    Frontiers in medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC
  5. Pathogenicity of Aspergillus nidulans isolated from the liver of diseased goat (Capra hircus)
    Nanchi Zhang, Yi Xiang, Junren Ding +6
    Brazilian Journal of MicrobiologyPeer-reviewedLicence not statedFull textInfectious diseasePMC

Cite

BibTeXRIS
BibTeX
@article{pang2026baseediting,
  title = {{A base-editing and auxotrophic selection platform for linking epigenetic regulators to silent biosynthetic gene clusters in Aspergillus nidulans.}},
  author = {Meng Pang and Donghui Guo and Yanling Li and Yuze Chen and Rumeng Du and Jiayang Liu and Jiahui Hu and Hang Li and Zhuofan Li and Guojun Pan and Yuan Tian and Fanglong Zhao},
  journal = {Synthetic and systems biotechnology},
  year = {2026},
  month = oct,
  doi = {10.1016/j.synbio.2026.10.001},
  url = {https://europepmc.org/article/MED/42904109},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - A base-editing and auxotrophic selection platform for linking epigenetic regulators to silent biosynthetic gene clusters in Aspergillus nidulans.
AU  - Meng Pang
AU  - Donghui Guo
AU  - Yanling Li
AU  - Yuze Chen
AU  - Rumeng Du
AU  - Jiayang Liu
AU  - Jiahui Hu
AU  - Hang Li
AU  - Zhuofan Li
AU  - Guojun Pan
AU  - Yuan Tian
AU  - Fanglong Zhao
PY  - 2026
DA  - 2026/10/13
JO  - Synthetic and systems biotechnology
DO  - 10.1016/j.synbio.2026.10.001
UR  - https://europepmc.org/article/MED/42904109
AB  - Filamentous fungi harbor numerous silent biosynthetic gene clusters (BGCs), representing an underexplored reservoir of natural products. Chemical inhibition of epigenetic regulators is an effective strategy for activating silent BGCs, but it often lacks specificity and cannot readily link activated clusters to their cognate regulators. Here, we developed a coupled cytosine base editing and auxotrophic selection platform in Aspergillus nidulans to systematically identify epigenetic regulators of silent gene clusters. An sgRNA library targeting 24 core epigenetic regulators was introduced, together with a cytosine base editor, into 21 pyrG-based PKS reporter strains, enabling growth-based selection and direct sgRNA recovery by Sanger sequencing. This screen identified five regulator-cluster activation pairs, including known interactions and two previously uncharacterized mechanisms. Specifically, KdmB represses the AN7084 gene cluster by erasing promoter H3K4me3, whereas Kmt5 silences the cichorine core pks gene through H4K20me3 deposition. This scalable platform enables rapid matching of silent BGCs with their epigenetic regulators and advances chromatin-guided fungal genome mining.
SN  - 2405-805X
ER  -