ArticleBMC biochemistry2009
Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate.
Article in BMC biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 38 citations in OpenAlex.
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them.Antibiotics (Basel, Switzerland) · 2022Review
- A Family of Nonribosomal Peptides Modulate Collective Behavior in Pseudovibrio Bacteria Isolated from Marine Sponges*.Angewandte Chemie (International ed. in English) · 2021Article
- Genetic platforms for heterologous expression of microbial natural products.Natural product reports · 2019Review
- Pseudomonas putida-a versatile host for the production of natural products.Applied microbiology and biotechnology · 2015Review
- Virulence determinants of Pseudomonas syringae strains isolated from grasses in the context of a small type III effector repertoire.BMC microbiology · 2014Article
- Production of proteasome inhibitor syringolin A by the endophyte Rhizobium sp. strain AP16.Applied and environmental microbiology · 2014Article
- Genomics-Based Exploration of Virulence Determinants and Host-Specific Adaptations of Pseudomonas syringae Strains Isolated from Grasses.Pathogens (Basel, Switzerland) · 2014Article
- High-Quality Draft Genome Sequence of Pseudomonas syringae pv. Syringae Strain SM, Isolated from Wheat.Genome announcements · 2013Article
- Pseudomonas syringae pv. syringae uses proteasome inhibitor syringolin A to colonize from wound infection sites.PLoS pathogens · 2013Article
- Enzymatic timing and tailoring of macrolactamization in syringolin biosynthesis.Organic letters · 2011Article
- Methods and options for the heterologous production of complex natural products.Natural product reports · 2011Review
- Proteasome activity imaging and profiling characterizes bacterial effector syringolin A.Plant physiology · 2011Article
- SylC catalyzes ureido-bond formation during biosynthesis of the proteasome inhibitor syringolin A.Journal of the American Chemical Society · 2009Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSyringolin A, an important virulence factor in the interaction of the phytopathogenic bacterium Pseudomonas syringae pv. syringae B728a with its host plant Phaseolus vulgaris (bean), was recently shown to irreversibly inhibit eukaryotic proteasomes by a novel mechanism. Syringolin A is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase and consists of a tripeptide part including a twelve-membered ring with an N-terminal valine that is joined to a second valine via a very unusual ureido group. Analysis of sequence and architecture of the syringolin A synthetase gene cluster with the five open reading frames sylA-sylE allowed to formulate a biosynthesis model that explained all structural features of the tripeptide part of syringolin A but left the biosynthesis of the unusual ureido group unaccounted for.
resultsWe have cloned a 22 kb genomic fragment containing the sylA-sylE gene cluster but no other complete gene into the broad host range cosmid pLAFR3. Transfer of the recombinant cosmid into Pseudomonas putida and P. syringae pv. syringae SM was sufficient to direct the biosynthesis of bona fide syringolin A in these heterologous organisms whose genomes do not contain homologous genes. NMR analysis of syringolin A isolated from cultures grown in the presence of NaH(13)CO(3) revealed preferential (13)C-labeling at the ureido carbonyl position.
conclusionThe results show that no additional syringolin A-specific genes were needed for the biosynthesis of the enigmatic ureido group joining two amino acids. They reveal the source of the ureido carbonyl group to be bicarbonate/carbon dioxide, which we hypothesize is incorporated by carbamylation of valine mediated by the sylC gene product(s). A similar mechanism may also play a role in the biosynthesis of other ureido-group-containing NRPS products known largely from cyanobacteria.
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