ArticleACS chemical biology2015
Genome-Directed Lead Discovery: Biosynthesis, Structure Elucidation, and Biological Evaluation of Two Families of Polyene Macrolactams against Trypanosoma brucei.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Gene amir_2071 of Actinosynnema mirum DSM 43827 encodes a dimethylallyltryptophan synthase superfamily protein responsible for the production of prenylated tyrosine.Folia microbiologica · 2026Article
- Article
- Karakum desert: a unique source of cultivable novel and rare actinomycetes with a remarkable biosynthetic potential.World journal of microbiology & biotechnology · 2025Article
- Exploring new natural products by utilizing untapped secondary metabolic pathways in actinomycetes.Journal of natural medicines · 2025Review
- Metabolomic and genomic insights into Micromonospora carbonacea subsp. caeruleus for anti-colorectal compound.Applied microbiology and biotechnology · 2025Article
- Marine Natural Products as Novel Treatments for Parasitic Diseases.Handbook of experimental pharmacology · 2025Review
- Exploring omics strategies for drug discovery fromFrontiers in pharmacology · 2025Review
- Biosynthesis of macrolactam antibiotics with β-amino acid polyketide starter units.The Journal of antibiotics · 2024Review
- The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-DerivedMarine drugs · 2024Article
- Uncovering the biotechnological capacity of marine and brackish water Planctomycetota.Antonie van Leeuwenhoek · 2024Article
- Genome mining for macrolactam-encoding gene clusters allowed for the network-guided isolation of β-amino acid-containing cyclic derivatives and heterologous production of ciromicin A.Communications chemistry · 2023Article
- Actinospica acidithermotolerans sp. nov., a novel actinomycete isolated from sediment from an Indonesian hot spring.Archives of microbiology · 2022Article
- Polyene Macrolactams from Marine and Terrestrial Sources: Structure, Production Strategies, Biosynthesis and Bioactivities.Marine drugs · 2022Review
- Activating cryptic biosynthetic gene cluster through a CRISPR-Cas12a-mediated direct cloning approach.Nucleic acids research · 2022Article
- Identification of Leucinostatins fromACS omega · 2022Article
- An isotopic labeling approach linking natural products with biosynthetic gene clusters.Nature chemical biology · 2022Article
- A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents.Biomolecules · 2021Review
- Microorganisms as a Potential Source of Molecules to Control Trypanosomatid Diseases.Molecules (Basel, Switzerland) · 2021Review
- Novel Macrolactams from a Deep-Sea-DerivedMarine drugs · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory activity against the protozoan parasite Trypanosoma brucei (lobosamide A IC50 = 0.8 μM), the causative agent of human African trypanosomiasis (HAT). The biosynthetic gene cluster of the lobosamides was sequenced and suggests a conserved cluster organization among the 26-membered macrolactams. While determination of the relative and absolute configurations of many members of this family is lacking, the absolute configurations of the lobosamides were deduced using a combination of chemical modification, detailed spectroscopic analysis, and bioinformatics. We implemented a "molecules-to-genes-to-molecules" approach to determine the prevalence of similar clusters in other bacteria, which led to the discovery of two additional macrolactams, mirilactams A and B from Actinosynnema mirum. These additional analogs have allowed us to identify specific structure-activity relationships that contribute to the antitrypanosomal activity of this class. This approach illustrates the power of combining chemical analysis and genomics in the discovery and characterization of natural products as new lead compounds for neglected disease targets.
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