{"doi":"10.1101/2023.10.26.564101","title":"Automated, self-resistance gene-guided, and high-throughput genome mining of bioactive natural products from <i>Streptomyces</i>","abstract":"Abstract Natural products (NPs) produced by bacteria, fungi and plants are a major source of drug leads. Streptomyces species are particularly important in this regard as they produce numerous natural products with prominent bioactivities. Here we report a fully a utomated, s calable and high-throughput platform for discovery of bioactive n atural p roducts in S treptomyces (FAST-NPS). This platform comprises computational prediction and prioritization of target biosynthetic gene clusters (BGCs) guided by self-resistance genes, highly efficient and automated direct cloning and heterologous expression of BGCs, followed by high-throughput fermentation and product extraction from Streptomyces strains. As a proof of concept, we applied this platform to clone 105 BGCs ranging from 10 to 100 kb that contain potential self-resistance genes from 11 Streptomyces strains with a success rate of 95%. Heterologous expression of all successfully cloned BGCs in Streptomyces lividans TK24 led to the discovery of 23 natural products from 12 BGCs. We selected 5 of these 12 BGCs for further characterization and found each of them could produce at least one natural product with antibacterial and/or anti-tumor activity, which resulted in a total of 8 bioactive natural products. Overall, this work would greatly accelerate the discovery of bioactive natural products for biomedical and biotechnological applications. Graphic Abstracts","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392710,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":306023,"name":"Chunshuai Huang","orcid":"0000-0002-3126-2340","position":1,"is_corresponding":false},{"id":436590,"name":"Nilmani Singh","orcid":"0000-0002-3684-7022","position":2,"is_corresponding":false},{"id":1131001,"name":"Guanhua Xun","orcid":"0000-0001-7211-4080","position":3,"is_corresponding":false},{"id":263533,"name":"Huimin Zhao","orcid":"0000-0002-9069-6739","position":4,"is_corresponding":false},{"id":1031084,"name":"Yujie Yuan","orcid":"0000-0001-5786-4377","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37961497","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}