Identification and Biosynthetic Study of the Siderophore Lysochelin in the Biocontrol Agent Lysobacter enzymogenes.

Lysobacter is a genus of bacteria emerging as new biocontrol agents in agriculture. Although iron acquisition is essential for the bacteria, no siderophore has been identified from any Lysobacter. Here, we report the identification of the first siderophore, N1,N8-bis(2,3-dihydroxybenzoyl)spermidine (lysochelin), and its biosynthetic gene cluster from Lysobacter enzymogenes. Intriguingly, the deletion of the spermidine biosynthetic gene encoding arginine decarboxylase or SAM decarboxylase eliminated lysochelin and the antifungals, HSAF and its analogues, which are key to the disease control activity and to the survival of Lysobacter under oxidative stresses caused by excess iron. The production of lysochelin and the antifungals is greatly affected by iron concentration. Together, the results revealed a previously unrecognized system, in which L. enzymogenes produces a group of small molecules, lysochelin, spermidine, and HSAF and its analogues, that are affected by iron concentration and critical to the growth and survival of the biocontrol agent.

[1]  Aaron T. Smith,et al.  Ferric iron reductases and their contribution to unicellular ferrous iron uptake. , 2021, Journal of inorganic biochemistry.

[2]  L. Du,et al.  Identification of the biosynthetic gene cluster for the anti-MRSA lysocins through gene cluster activation using strong promoters of housekeeping genes and production of new analogs in Lysobacter sp. 3655. , 2020, ACS synthetic biology.

[3]  Yuemao Shen,et al.  Identification of an Anti-MRSA Cyclic Lipodepsipeptide, WBP-29479A1, by Genome Mining of Lysobacter antibioticus. , 2019, Organic letters.

[4]  S. Chou,et al.  Spermidine plays a significant role in stabilizing a master transcription factor Clp to promote antifungal activity in Lysobacter enzymogenes , 2019, Applied Microbiology and Biotechnology.

[5]  L. Du,et al.  Spermidine-Regulated Biosynthesis of Heat-Stable Antifungal Factor (HSAF) in Lysobacter enzymogenes OH11 , 2018, Front. Microbiol..

[6]  M. Moore,et al.  Ironing out siderophore biosynthesis: a review of non-ribosomal peptide synthetase (NRPS)-independent siderophore synthetases , 2018, Critical reviews in biochemistry and molecular biology.

[7]  Yuemao Shen,et al.  Biosynthesis of the Polycyclic System in the Antifungal HSAF and Analogues from Lysobacter enzymogenes. , 2018, Angewandte Chemie.

[8]  F. Morel,et al.  The purple non‐sulfur bacterium Rhodopseudomonas palustris produces novel petrobactin‐related siderophores under aerobic and anaerobic conditions , 2018, Environmental microbiology.

[9]  L. Du,et al.  Functional and Structural Analysis of Phenazine O-Methyltransferase LaPhzM from Lysobacter antibioticus OH13 and One-Pot Enzymatic Synthesis of the Antibiotic Myxin. , 2018, ACS chemical biology.

[10]  Guido Kroemer,et al.  Spermidine in health and disease , 2018, Science.

[11]  K. Sekimizu,et al.  Lysobacter species: a potential source of novel antibiotics , 2016, Archives of Microbiology.

[12]  Haotong Chen,et al.  Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus. , 2016, Organic letters.

[13]  Kate Campbell,et al.  Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell. , 2015, Journal of molecular biology.

[14]  Stephen J. Wright,et al.  Bioactive Polycyclic Tetramate Macrolactams from Lysobacter enzymogenes and Their Absolute Configurations by Theoretical ECD Calculations. , 2015, Journal of natural products.

[15]  Yansheng Wang,et al.  Transcriptomic analysis reveals new regulatory roles of Clp signaling in secondary metabolite biosynthesis and surface motility in Lysobacter enzymogenes OH11 , 2014, Applied Microbiology and Biotechnology.

[16]  Haotong Chen,et al.  Iterative assembly of two separate polyketide chains by the same single-module bacterial polyketide synthase in the biosynthesis of HSAF. , 2014, Angewandte Chemie.

[17]  Yuemao Shen,et al.  Bioactive natural products from Lysobacter. , 2012, Natural product reports.

[18]  M. Nett,et al.  Structure and biosynthetic assembly of cupriachelin, a photoreactive siderophore from the bioplastic producer Cupriavidus necator H16. , 2012, Journal of the American Chemical Society.

[19]  M. Marahiel,et al.  Biosynthesis of the siderophore rhodochelin requires the coordinated expression of three independent gene clusters in Rhodococcus jostii RHA1. , 2011, Journal of the American Chemical Society.

[20]  K. Zaleta-Rivera,et al.  Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes. , 2011, Journal of the American Chemical Society.

[21]  G. Challis.  Genome mining for novel natural product discovery. , 2008, Journal of medicinal chemistry.

[22]  L. Osborne,et al.  Fusarium head blight biological control with Lysobacter enzymogenes strain C3 , 2006 .

[23]  L. Du,et al.  Distinct ceramide synthases regulate polarized growth in the filamentous fungus Aspergillus nidulans. , 2005, Molecular biology of the cell.

[24]  Sylvie Lautru,et al.  Discovery of a new peptide natural product by Streptomyces coelicolor genome mining , 2005, Nature chemical biology.

[25]  P. Delepelaire,et al.  Bacterial iron sources: from siderophores to hemophores. , 2004, Annual review of microbiology.

[26]  C. Walsh,et al.  Vibriobactin biosynthesis in Vibrio cholerae: VibH is an amide synthase homologous to nonribosomal peptide synthetase condensation domains. , 2000, Biochemistry.

[27]  F. D. Cook,et al.  Lysobacter, a New Genus of Nonfruiting, Gliding Bacteria with a High Base Ratio , 1978 .

[28]  J. Neilands,et al.  Universal chemical assay for the detection and determination of siderophores. , 1987, Analytical biochemistry.

[29]  G. H. Tait.  The identification and biosynthesis of siderochromes formed by Micrococcus denitrificans. , 1975, The Biochemical journal.

[30]  G. Anderegg,et al.  Hydroxamatkomplexe III. Eisen(III)‐Austausch zwischen Sideraminen und Komplexonen. Diskussion der Bildungskonstanten der Hydroxamatkomplexe , 1963 .