Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus Subtilis ATCC6633

Overview

Journal Chem Biol

Publisher Elsevier

Specialties Biochemistry
Biology
Chemistry

Date 2010 Feb 10

PMID 20142038

Citations 44

Authors

Svetlana A Borisova

Benjamin T Circello

Jun Kai Zhang

Wilfred A van der Donk

William W Metcalf

Affiliations

Soon will be listed here.

Abstract

Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway.

Citing Articles

Whole-Genome Profiling of Endophytic Strain B.L.Ns.14 from Reveals Potential for Agricultural Bioenhancement.

Douka D, Spantidos T, Tsalgatidou P, Katinakis P, Venieraki A Microorganisms. 2025; 12(12.

PMID: 39770806 PMC: 11678546. DOI: 10.3390/microorganisms12122604.

Biosynthesis of Phosphonoalamides Reveals Highly Specific Amino Acid Ligation.

Cui J, Ju K ACS Chem Biol. 2024; 19(7):1506-1514.

PMID: 38885091 PMC: 11259534. DOI: 10.1021/acschembio.4c00190.

Phosphonoalamides Reveal the Biosynthetic Origin of Phosphonoalanine Natural Products and a Convergent Pathway for Their Diversification.

Cui J, Zhang Y, Ju K Angew Chem Int Ed Engl. 2024; 63(32):e202405052.

PMID: 38780891 PMC: 11867202. DOI: 10.1002/anie.202405052.

Discovery of Antimicrobial Phosphonopeptide Natural Products from Bacillus velezensis by Genome Mining.

Wilson J, Cui J, Nakao T, Kwok H, Zhang Y, Kayrouz C Appl Environ Microbiol. 2023; 89(6):e0033823.

PMID: 37377428 PMC: 10304907. DOI: 10.1128/aem.00338-23.

A Novel Pathway for Biosynthesis of the Herbicidal Phosphonate Natural Product Phosphonothrixin Is Widespread in Actinobacteria.

Bown L, Hirota R, Goettge M, Cui J, Krist D, Zhu L J Bacteriol. 2023; 205(5):e0048522.

PMID: 37074199 PMC: 10210982. DOI: 10.1128/jb.00485-22.

References

Woodyer R, Shao Z, Thomas P, Kelleher N, Blodgett J, Metcalf W . Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster. Chem Biol. 2006; 13(11):1171-82. DOI: 10.1016/j.chembiol.2006.09.007. View

Galperin M, Koonin E . A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci. 1998; 6(12):2639-43. PMC: 2143612. DOI: 10.1002/pro.5560061218. View

Kugler M, Loeffler W, Rapp C, Kern A, Jung G . Rhizocticin A, an antifungal phosphono-oligopeptide of Bacillus subtilis ATCC 6633: biological properties. Arch Microbiol. 1990; 153(3):276-81. DOI: 10.1007/BF00249082. View

Kino K, Noguchi A, Nakazawa Y, Yagasaki M . A novel l-amino acid ligase from bacillus licheniformis. J Biosci Bioeng. 2008; 106(3):313-5. DOI: 10.1263/jbb.106.313. View

Maddocks S, Oyston P . Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology (Reading). 2008; 154(Pt 12):3609-3623. DOI: 10.1099/mic.0.2008/022772-0. View

Seidel H, Freeman S, Seto H, Knowles J . Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond. Nature. 1988; 335(6189):457-8. DOI: 10.1038/335457a0. View

Artymiuk P, Poirrette A, Rice D, Willett P . Biotin carboxylase comes into the fold. Nat Struct Biol. 1996; 3(2):128-32. DOI: 10.1038/nsb0296-128. View

Fan C, Moews P, WALSH C, Knox J . Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994; 266(5184):439-43. DOI: 10.1126/science.7939684. View

Blodgett J, Zhang J, Metcalf W . Molecular cloning, sequence analysis, and heterologous expression of the phosphinothricin tripeptide biosynthetic gene cluster from Streptomyces viridochromogenes DSM 40736. Antimicrob Agents Chemother. 2004; 49(1):230-40. PMC: 538901. DOI: 10.1128/AAC.49.1.230-240.2005. View

10.

Manjasetty B, Powlowski J, Vrielink A . Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate. Proc Natl Acad Sci U S A. 2003; 100(12):6992-7. PMC: 165818. DOI: 10.1073/pnas.1236794100. View

11.

Ose T, Watanabe K, Mie T, Honma M, Watanabe H, Yao M . Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase. Nature. 2003; 422(6928):185-9. DOI: 10.1038/nature01454. View

12.

Yamaguchi H, Kato H, Hata Y, Nishioka T, Kimura A, Oda J . Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. J Mol Biol. 1993; 229(4):1083-100. DOI: 10.1006/jmbi.1993.1106. View

13.

Mehta P, Hale T, Christen P . Aminotransferases: demonstration of homology and division into evolutionary subgroups. Eur J Biochem. 1993; 214(2):549-61. DOI: 10.1111/j.1432-1033.1993.tb17953.x. View

14.

Diddens H, Dorgerloh M, Zahner H . Metabolic products of microorganisms. 176. On the transport of small peptide antibiotics in bacteria. J Antibiot (Tokyo). 1979; 32(1):87-90. DOI: 10.7164/antibiotics.32.87. View

15.

Kelley L, Sternberg M . Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009; 4(3):363-71. DOI: 10.1038/nprot.2009.2. View

16.

Kino K, Nakazawa Y, Yagasaki M . Dipeptide synthesis by L-amino acid ligase from Ralstonia solanacearum. Biochem Biophys Res Commun. 2008; 371(3):536-40. DOI: 10.1016/j.bbrc.2008.04.105. View

17.

Cicchillo R, Zhang H, Blodgett J, Whitteck J, Li G, Nair S . An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature. 2009; 459(7248):871-4. PMC: 2874955. DOI: 10.1038/nature07972. View

18.

MICHENER H, SNELL N . Two antifungal substances from Bacillus subtilis cultures. Arch Biochem. 1949; 22(2):208-14. View

19.

Schell M . Molecular biology of the LysR family of transcriptional regulators. Annu Rev Microbiol. 1993; 47:597-626. DOI: 10.1146/annurev.mi.47.100193.003121. View

20.

Higgins L, Yan F, Liu P, Liu H, Drennan C . Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme. Nature. 2005; 437(7060):838-44. DOI: 10.1038/nature03924. View