Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes

Lili Lou, Guoliang Qian, Yunxuan Xie, Jiliang Hang, Haotong Chen, Kathia Zaleta-Rivera, Yaoyao Li, Yuemao Shen, Patrick H. Dussault, Fengquan Liu, Liangcheng Du

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here we describe the HSAF biosynthetic gene cluster, which contains only a single-module polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/NRPS are six genes that encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activates L-ornithine and that the four-domain NRPS is able to catalyze the formation of a tetramic acid-containing product from acyl-S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms.

Original languageEnglish (US)
Pages (from-to)643-645
Number of pages3
JournalJournal of the American Chemical Society
Volume133
Issue number4
DOIs
StatePublished - Feb 2 2011

Fingerprint

Lysobacter
Biosynthesis
Peptide Synthases
Polyketide Synthases
Genes
Fatty Acid Desaturases
Peptides
Ornithine
Acids
Sterols
Mixed Function Oxygenases
Fatty acids
Oxidation-Reduction
Polyketides
Ferredoxins
Sphingolipids
Gene encoding
Mycoses
Multigene Family
Fungi

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes. / Lou, Lili; Qian, Guoliang; Xie, Yunxuan; Hang, Jiliang; Chen, Haotong; Zaleta-Rivera, Kathia; Li, Yaoyao; Shen, Yuemao; Dussault, Patrick H.; Liu, Fengquan; Du, Liangcheng.

In: Journal of the American Chemical Society, Vol. 133, No. 4, 02.02.2011, p. 643-645.

Research output: Contribution to journalArticle

Lou, L, Qian, G, Xie, Y, Hang, J, Chen, H, Zaleta-Rivera, K, Li, Y, Shen, Y, Dussault, PH, Liu, F & Du, L 2011, 'Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes', Journal of the American Chemical Society, vol. 133, no. 4, pp. 643-645. https://doi.org/10.1021/ja105732c
Lou, Lili ; Qian, Guoliang ; Xie, Yunxuan ; Hang, Jiliang ; Chen, Haotong ; Zaleta-Rivera, Kathia ; Li, Yaoyao ; Shen, Yuemao ; Dussault, Patrick H. ; Liu, Fengquan ; Du, Liangcheng. / Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 4. pp. 643-645.
@article{26980f5b0e5841d68e9e9961b77353b1,
title = "Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes",
abstract = "HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here we describe the HSAF biosynthetic gene cluster, which contains only a single-module polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/NRPS are six genes that encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activates L-ornithine and that the four-domain NRPS is able to catalyze the formation of a tetramic acid-containing product from acyl-S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms.",
author = "Lili Lou and Guoliang Qian and Yunxuan Xie and Jiliang Hang and Haotong Chen and Kathia Zaleta-Rivera and Yaoyao Li and Yuemao Shen and Dussault, {Patrick H.} and Fengquan Liu and Liangcheng Du",
year = "2011",
month = "2",
day = "2",
doi = "10.1021/ja105732c",
language = "English (US)",
volume = "133",
pages = "643--645",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes

AU - Lou, Lili

AU - Qian, Guoliang

AU - Xie, Yunxuan

AU - Hang, Jiliang

AU - Chen, Haotong

AU - Zaleta-Rivera, Kathia

AU - Li, Yaoyao

AU - Shen, Yuemao

AU - Dussault, Patrick H.

AU - Liu, Fengquan

AU - Du, Liangcheng

PY - 2011/2/2

Y1 - 2011/2/2

N2 - HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here we describe the HSAF biosynthetic gene cluster, which contains only a single-module polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/NRPS are six genes that encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activates L-ornithine and that the four-domain NRPS is able to catalyze the formation of a tetramic acid-containing product from acyl-S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms.

AB - HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here we describe the HSAF biosynthetic gene cluster, which contains only a single-module polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/NRPS are six genes that encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activates L-ornithine and that the four-domain NRPS is able to catalyze the formation of a tetramic acid-containing product from acyl-S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms.

UR - http://www.scopus.com/inward/record.url?scp=79851497066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79851497066&partnerID=8YFLogxK

U2 - 10.1021/ja105732c

DO - 10.1021/ja105732c

M3 - Article

C2 - 21171605

AN - SCOPUS:79851497066

VL - 133

SP - 643

EP - 645

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 4

ER -