ArticleChemistry & biology2011
Selective overproduction of the proteasome inhibitor salinosporamide A via precursor pathway regulation.
Article in Chemistry & biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae.Applied and environmental microbiology · 2023Article
- Studies on Streptomyces sp. SN-593: reveromycin biosynthesis, β-carboline biomediator activating LuxR family regulator, and construction of terpenoid biosynthetic platform.The Journal of antibiotics · 2022Review
- Use of genome-scale models to get new insights into the marine actinomycete genus Salinispora.BMC systems biology · 2019Article
- Engineering Salinispora tropica for heterologous expression of natural product biosynthetic gene clusters.Applied microbiology and biotechnology · 2018Article
- Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds.Frontiers in microbiology · 2017Review
- The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery.Natural product reports · 2015Review
- Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species.Chemistry & biology · 2015Article
- Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin.Journal of natural products · 2015Article
- Identification of a fluorometabolite fromChemical science · 2015Article
- Article
- Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Challenges and triumphs to genomics-based natural product discovery.Journal of industrial microbiology & biotechnology · 2014Article
- Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development.Marine drugs · 2014Review
- Genetic complementation of the obligate marine actinobacterium Salinispora tropica with the large mechanosensitive channel gene mscL rescues cells from osmotic downshock.Applied and environmental microbiology · 2012Article
- Lessons from the past and charting the future of marine natural products drug discovery and chemical biology.Chemistry & biology · 2012Review
- A walk into the LuxR regulators of Actinobacteria: phylogenomic distribution and functional diversity.PloS one · 2012Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The chlorinated natural product salinosporamide A is a potent 20S proteasome inhibitor currently in clinical trials as an anticancer agent. To deepen our understanding of salinosporamide biosynthesis, we investigated the function of a LuxR-type pathway-specific regulatory gene, salR2, and observed a selective effect on the production of salinosporamide A over its less active aliphatic analogs. SalR2 specifically activates genes involved in the biosynthesis of the halogenated precursor chloroethylmalonyl-CoA, which is a dedicated precursor of salinosporamide A. Specifically, SalR2 activates transcription of two divergent operons-one of which contains the unique S-adenosyl-L-methionine-dependent chlorinase encoding gene salL. By applying this knowledge to rational engineering, we were able to selectively double salinosporamide A production. This study exemplifies the specialized regulation of a polyketide precursor pathway and its application to the selective overproduction of a specific natural product congener.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.