Evidence map›Paper›PMID 24153004›Full record

ArticleOpen biology2013

Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin.

Roman Makitrynskyy, Bohdan Ostash, Olga Tsypik, Yuriy Rebets, Emma Doud, Timothy Meredith, Andriy Luzhetskyy, Andreas Bechthold, Suzanne Walker, Victor Fedorenko

Open access · goldAbstract read
In one paragraph

Article in Open biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Roman MakitrynskyyDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, Hrushevskoho st. 4, Lviv 79005, Ukraine.
Bohdan Ostash
Olga Tsypik
Yuriy Rebets
Emma Doud
Timothy Meredith
Andriy Luzhetskyy
Andreas Bechthold
Suzanne Walker
Victor Fedorenko
Harvard University · USLviv University · UAUniversity of Freiburg · DE

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
Enabling Biotechnologies to Generate Novel Phosphoglycolipid AntibioticsR03TW009424 · FIC · HARVARD MEDICAL SCHOOL · PI WALKER, SUZANNE · 2013 to 2015
$135k
FIC NIH HHS R03 TW009424FIC NIH HHS R03TW009424NIAID NIH HHS 2P01AI083214-04NIAID NIH HHS T32 AI007061
6 · The paper itself

Abstract

Unlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs). This raises questions about the regulatory signals that initiate and sustain moenomycin production. We now show that three pleiotropic regulatory genes for Streptomyces morphogenesis and antibiotic production-bldA, adpA and absB-exert multi-layered control over moenomycin biosynthesis in native and heterologous producers. The bldA gene for tRNA(Leu)UAA is required for the translation of rare UUA codons within two key moenomycin biosynthetic genes (moe), moeO5 and moeE5. It also indirectly influences moenomycin production by controlling the translation of the UUA-containing adpA and, probably, other as-yet-unknown repressor gene(s). AdpA binds key moe promoters and activates them. Furthermore, AdpA interacts with the bldA promoter, thus impacting translation of bldA-dependent mRNAs-that of adpA and several moe genes. Both adpA expression and moenomycin production are increased in an absB-deficient background, most probably because AbsB normally limits adpA mRNA abundance through ribonucleolytic cleavage. Our work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs. This strategy might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining.

Indexed as

Genes, BacterialGenes, RegulatorAnti-Bacterial AgentsBacterial ProteinsCodonComputer SimulationGene Expression Regulation, BacterialGenome, BacterialMutationOligosaccharidesPeptidoglycan GlycosyltransferasePromoter Regions, GeneticRNA, BacterialRNA, Transfer, LeuSecondary MetabolismSignal TransductionAnti-Bacterial AgentsBacterial ProteinsCodonmoenomycinOligosaccharidesPeptidoglycan GlycosyltransferaseRNA, BacterialRNA, Transfer, LeuTrans-ActivatorsabsBadpAbldAmoenomycin Apleiotropic regulatorsStreptomyces

Identifiers

PMID24153004
PMCPMC3814723
OpenAlexW2126389156

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.