title: Phosphate starvation in fungi induces the replacement of phosphatidylcholine with the phosphorus-free betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine.
abstract: Diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) is a phosphorus-free betaine-lipid analog of phosphatidylcholine (PtdCho) synthesized by many soil bacteria, algae, and nonvascular plants. Synthesis of DGTS and other phosphorus-free lipids in bacteria occurs in response to phosphorus (P) deprivation and results in the replacement of phospholipids by nonphosphorous lipids. The genes encoding DGTS biosynthetic enzymes have previously been identified and characterized in bacteria and the alga Chlamydomonas reinhardtii. We now report that many fungal genomes, including those of plant and animal pathogens, encode the enzymatic machinery for DGTS biosynthesis, and that fungi synthesize DGTS during P limitation. This finding demonstrates that replacement of phospholipids by nonphosphorous lipids is a strategy used in divergent eukaryotic lineages for the conservation of P under P-limiting conditions. Mutants of Neurospora crassa were used to show that DGTS synthase encoded by the BTA1 gene is solely responsible for DGTS biosynthesis and is under the control of the fungal phosphorus deprivation regulon, mediated by the NUC-1/Pho4p transcription factor. Furthermore, we describe the rational reengineering of lipid metabolism in the yeast Saccharomyces cerevisiae, such that PtdCho is completely replaced by DGTS, and demonstrate that essential processes of membrane biogenesis and organelle assembly are functional and support growth in the engineered strain.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, USA School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA wriekhof2@unl.edu.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Riekhof
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Naik
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Helmut
authors.initials: H
authors.lastname: Bertrand
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Benning
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D007716:Kluyveromyces / Q000235:genetics / Q000378:metabolism*; D009492:Neurospora crassa / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000172:deficiency* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C021660:1(3),2-diacylglyceryl-3(1)-O-4'-(N,N,N-trimethyl)homoserine; D005656:Fungal Proteins; D010710:Phosphates; D010713:Phosphatidylcholines; D014280:Triglycerides
references.citation: Methods Enzymol. 1991;194:795-823
references.pmid: 2005825
references.citation: Curr Genet. 2013 Nov;59(4):231-42
references.pmid: 24057105
references.citation: PLoS Pathog. 2013 Mar;9(3):e1003210
references.pmid: 23505370
references.citation: Methods Enzymol. 2002;350:87-96
references.pmid: 12073338
references.citation: Genetics. 1998 Dec;150(4):1349-59
references.pmid: 9832515
references.citation: J Biol Chem. 2005 Apr 1;280(13):12461-6
references.pmid: 15664981
references.citation: J Biol Chem. 2005 Jan 28;280(4):2397-400
references.pmid: 15590685
references.citation: Genetics. 2001 Dec;159(4):1491-9
references.pmid: 11779791
references.citation: Arch Biochem Biophys. 2005 Sep 1;441(1):96-105
references.pmid: 16095555
references.citation: Biochim Biophys Acta. 1991 Feb 26;1082(1):108-11
references.pmid: 2009297
references.citation: Eukaryot Cell. 2005 Feb;4(2):242-52
references.pmid: 15701786
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10649-54
references.pmid: 10973486
references.citation: Prog Lipid Res. 2013 Jan;52(1):43-50
references.pmid: 22954597
references.citation: Lipids. 1976 Oct;11(10):778-80
references.pmid: 136584
references.citation: Biochim Biophys Acta. 1999 Jul 30;1439(2):167-74
references.pmid: 10425393
references.citation: PLoS Genet. 2010 Aug 19;6(8):e1001070
references.pmid: 20808890
references.citation: Nature. 2009 Mar 5;458(7234):69-72
references.pmid: 19182781
references.citation: Science. 1994 Feb 25;263(5150):1153-6
references.pmid: 8108735
references.citation: Mol Cell Biol. 1994 Dec;14(12):7816-26
references.pmid: 7969122
references.citation: Fungal Genet Biol. 1996 Sep;20(3):185-91
references.pmid: 8953266
references.citation: Mol Cell. 2008 Feb 1;29(2):191-206
references.pmid: 18243114
references.citation: J Biol Chem. 1993 Oct 5;268(28):21416-24
references.pmid: 8407984
references.citation: J Cell Biol. 1995 Mar;128(5):779-92
references.pmid: 7533169
references.citation: Gene. 1996 Nov 7;179(1):171-7
references.pmid: 8955644
references.citation: Mol Cell Biol. 1990 Nov;10(11):5839-48
references.pmid: 2146493
references.citation: Mol Plant Microbe Interact. 2005 Sep;18(9):973-82
references.pmid: 16167767
references.citation: J Biol Chem. 2004 Oct 1;279(40):42321-30
references.pmid: 15269223
references.citation: Science. 2010 Jul 9;329(5988):223-6
references.pmid: 20616280
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10352-10357
references.pmid: 16801547
references.citation: J Biol Chem. 1998 Jul 3;273(27):16635-8
references.pmid: 9642212
references.citation: J Biol Chem. 2007 Dec 21;282(51):36853-61
references.pmid: 17951629
references.citation: Methods Mol Biol. 2010;638:33-40
references.pmid: 20238259
references.citation: PLoS One. 2012;7(1):e30119
references.pmid: 22253901
references.citation: Trends Plant Sci. 2005 Jan;10(1):22-9
references.pmid: 15642520
references.citation: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5910-5
references.pmid: 11331765
references.citation: Adv Appl Microbiol. 2003;52:245-62
references.pmid: 12964247
references.citation: Yeast. 1998 Jan 30;14(2):115-32
references.pmid: 9483801
references.citation: Phytochemistry. 1997 Nov;46(5):883-92
references.pmid: 9375419
references.citation: Arch Biochem Biophys. 1995 Feb 20;317(1):103-11
references.pmid: 7872771