{"doi":"10.1016/j.jbc.2021.101047","title":"Anti-Zika candidates from a marine fungus with a remarkable biosynthetic repertoire","abstract":"The study of natural products provides exciting opportunities for the discovery of novel biologically active molecules and biosynthetic pathways. Recently, Yuan and colleagues described 30 cyclic depsipeptides that are biosynthesized by proteins encoded by three distinct gene clusters in the marine fungus, Beauveria felina. Genetic and biochemical studies confirmed the involvement of nonribosomal peptide synthetases in the production of multiple compounds, some of which inhibit Zika virus replication. The study of natural products provides exciting opportunities for the discovery of novel biologically active molecules and biosynthetic pathways. Recently, Yuan and colleagues described 30 cyclic depsipeptides that are biosynthesized by proteins encoded by three distinct gene clusters in the marine fungus, Beauveria felina. Genetic and biochemical studies confirmed the involvement of nonribosomal peptide synthetases in the production of multiple compounds, some of which inhibit Zika virus replication. Recent outbreaks caused by Zika virus, a member of the positive strand RNA flavivirus genus, have caused alarm notably due to the transmissibility of the virus across the placental barrier. Vaccines against Zika virus are still under development, and there are currently no approved antiviral treatments. Microbial natural products are an important source and inspiration for the development of novel pharmaceuticals, including as antiviral compounds (1Musarra-Pizzo M. Pennisi R. Ben-Amor I. Mandalari G. Sciortino M.T. Antiviral activity exerted by natural products against human viruses.Viruses. 2021; 13: 828Crossref PubMed Scopus (14) Google Scholar). Many natural products originally identified during a period of in-depth investigation between the 1960s and 1980s are now being reexamined following advances in microbial culturing and genomic sequencing, as well as advances in biochemical and heterologous methods for production of these compounds. During the past decade, our understanding of the biosynthesis pathways that produce these compounds has increased, helping to realize the long-standing goal of predicting products from gene sequences and engineering or combining catalysts from different biosynthetic gene clusters to produce novel compounds with desirable activities (2Medema M.H. The year 2020 in natural product bioinformatics: An overview of the latest tools and databases.Nat. Prod. Rep. 2021; 38: 301-306Crossref PubMed Google Scholar). Many peptide natural products are produced by the nonribosomal peptide synthetases (NRPSs), a family of megasynthetase proteins that produce peptides using an unusual enzymatic architecture. Generally, NRPSs consist of fused catalytic domains that function with an assembly line strategy to produce a variety of peptide natural products, including antibiotics, siderophores, signaling molecules, toxins, and antitumor molecules (3Bonhomme S. Dessen A. Macheboeuf P. The inherent flexibility of type I non-ribosomal peptide synthetase multienzymes drives their catalytic activities.Open Biol. 2021; 11: 200386Crossref PubMed Scopus (1) Google Scholar). Independent of ribosomes, mRNAs, and tRNAs, the NRPS enzymes can incorporate nonproteinogenic amino acids into their products. An important class of NRPS products is the cyclodepsipeptides (CDPs), which are cyclic arrangements of amino and hydroxy acids joined with amide and ester bonds (4Sivanathan S. Scherkenbeck J. Cyclodepsipeptides: A rich source of biologically active compounds for drug research.Molecules. 2014; 19: 12368-12420Crossref PubMed Scopus (59) Google Scholar). One family of cyclohexadepsipeptides includes destruxins (DTXs), isaridins (ISDs), and isariins (ISRs), which all contain six building blocks, including one β-amino or β-hydroxy acid, to form a 19-membered macrocycle. Multiple DTX, ISD, and ISR analogs exhibit diverse insecticidal, antifungal, antiviral, and antibacterial activities, and understanding the enzymatic basis of CDP biosy","journal":"Journal of Biological Chemistry","year":2021,"id":208448,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473664,"name":"Andrew M. Gulick","orcid":"0000-0003-4238-7453","position":1,"is_corresponding":false},{"id":795048,"name":"Ketan D. Patel","orcid":"0000-0003-4254-3145","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:51:57.582057Z","pmid":"34358564","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":[]}