1887

Abstract

The filamentous fungus provides a renewable biosource of industrial high-value compounds such as carotenes, other isoprenoids (ubiquinone and sterols), organic acids and fatty acids. Several mutants involved in the formation of β-carotene are available. For example, the mutants have a leaky mutation in the phytoene synthase and produce significantly lower amounts of carotenes, while the and mutants produce phytoene and lycopene, respectively, due to a null mutation in the genes encoding the phytoene dehydrogenase and lycopene cyclase, respectively. The S mutants are mutated in the gene encoding the oxygenase responsible for the conversion of β-carotene into apocarotenoids and, as a result, β-carotene accumulates. In order to ascertain further the biochemical changes arising in these potential industrial strains, a metabolite profiling workflow was implemented for . GC-MS and ultra-performance liquid chromatography–photodiode array platforms enabled the identification of over 100 metabolites in 11 , , and mutant strains and their wild-type comparator. All mutant strains possessed decreased TCA cycle intermediates, galactose, alanine and ribitol, while dodecanol and valine showed a general increase. As predicted, other terpenoid levels were affected in the , and mutants but not in the mutants. The global changes across intermediary metabolism of the mutants suggest that complex metabolic networks exist between intermediary and secondary metabolism or that other mutations beyond the carotene pathway may exist in these mutants. These data show the utility of the methodology in metabolically phenotyping strains with potential industrial exploitation.

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2016-11-23
2020-03-29
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References

  1. Arrach N., Fernández-Martín R., Cerdá-Olmedo E., Avalos J.. 2001; A single gene for lycopene cyclase, phytoene synthase, and regulation of carotene biosynthesis in Phycomyces. Proc Natl Acad Sci USA98:1687–1692 [CrossRef][PubMed]
    [Google Scholar]
  2. Barrero A. F., Oltra J. E., Poyatos J. A., Jiménez D., Oliver E., Enrique Oltra J.. 1998; Phycomysterols and other sterols from the fungus Phycomyces blakesleeanus. J Nat Prod61:1491–1496 [CrossRef][PubMed]
    [Google Scholar]
  3. Barrero A. F., Oltra J. E., Robinson J., Burke P. V., Jiménez D., Oliver E., Enrique Oltra J.. 2002; Sterols in erg mutants of Phycomyces: metabolic pathways and physiological effects. Steroids67:403–409 [CrossRef][PubMed]
    [Google Scholar]
  4. Bejarano E. R., Parra F., Murillo F. J., Cerd-Olmedo E.. 1988; End-product regulation of carotenogenesis in Phycomyces. Arch Microbiol150:209–214 [CrossRef]
    [Google Scholar]
  5. Benjamini Y., Hochberg Y.. 1995; Controlling the false discovery rate: a practical and powerful approach to multiple testing. JR Stat Soc Ser B57:289–300
    [Google Scholar]
  6. Bergman K., Eslava A. P., Cerdá-Olmedo E.. 1973; Mutants of Phycomyces with abnormal phototropism. Mol Gen Genet123:1–16 [CrossRef][PubMed]
    [Google Scholar]
  7. Bino R. J., Hall R. D., Fiehn O., Kopka J., Saito K., Draper J., Nikolau B. J., Mendes P., Roessner-Tunali U. et al. 2004; Potential of metabolomics as a functional genomics tool. Trends Plant Sci9:418–425 [CrossRef][PubMed]
    [Google Scholar]
  8. Cazzonelli C. I., Pogson B. J.. 2010; Source to sink: regulation of carotenoid biosynthesis in plants. Trends Plant Sci15:266–274 [CrossRef][PubMed]
    [Google Scholar]
  9. Cerdá-Olmedo E.. 1987; Standard growth conditions and variations. In Phycomyces , pp.337–339 Edited by Cerdá-Olmedo E., Lipson E. D.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  10. Cerdá-Olmedo E.. 2001; Phycomyces and the biology of light and color. FEMS Microbiol Rev25:503–512 [CrossRef][PubMed]
    [Google Scholar]
  11. Cherubini F.. 2010; The biorefinery concept: using biomass instead of oil for producing energy and chemicals. Energy Convers Manage51:1412–1421 [CrossRef]
    [Google Scholar]
  12. Chichester C. O., Yokoyama H., Nakayama T. O., Lukton A., Mackinney G.. 1959; Leucine metabolism and carotene biosynthesis. J Biol Chem234:598–602[PubMed]
    [Google Scholar]
  13. Clark J. H., Luque R., Matharu A. S.. 2012; Green chemistry, biofuels, and biorefinery. Annu Rev Chem Biomol Eng3:183–207 [CrossRef][PubMed]
    [Google Scholar]
  14. Connor M. R., Atsumi S.. 2010; Synthetic biology guides biofuel production. J Biomed Biotechnol2010:1–9 [CrossRef]
    [Google Scholar]
  15. Corrochano L. M., Cerdá-Olmedo E.. 1992; Sex, light and carotenes: the development of Phycomyces. Trends Genet8:268–274 [CrossRef][PubMed]
    [Google Scholar]
  16. Corrochano L. M., Kuo A., Marcet-Houben M., Polaino S., Salamov A., Villalobos-Escobedo J. M., Grimwood J., Álvarez M. I., Avalos J. et al. 2016; Expansion of signal transduction pathways in fungi by extensive genome duplication. Curr Biol26:1577–1584 [CrossRef][PubMed]
    [Google Scholar]
  17. DeBell R. M., Jack R. C.. 1975; Stereospecific analysis of major glycerolipids of Phycomyces blakesleeanus sporangiophores and mycelium. J Bacteriol124:220–224[PubMed]
    [Google Scholar]
  18. Eslava A. P.. 1987; Genetics. In Phycomyces , pp.27–48Edited by Cerdá-Olmedo E., Lipson E. D.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  19. Eslava A. P., Cerdá-Olmedo E.. 1974; Genetic control of phytoene dehydrogenation in Phycomyces. Plant Sci Lett2:9–14 [CrossRef]
    [Google Scholar]
  20. Fesenko E., Edwards R.. 2014; Plant synthetic biology: a new platform for industrial biotechnology. J Exp Bot65:1927–1937 [CrossRef][PubMed]
    [Google Scholar]
  21. Goodwin T. W., Lijinsky W.. 1951; Studies in carotenogenesis. II. Carotene production by Phycomyces blakesleeanus: the effect of different amino acids when used in media containing low concentrations of glucose. Biochem J50:268–273 [CrossRef][PubMed]
    [Google Scholar]
  22. Gruszecki W. I., Strzałka K.. 2005; Carotenoids as modulators of lipid membrane physical properties. Biochim Biophys Acta1740:108–115 [CrossRef][PubMed]
    [Google Scholar]
  23. Halket J. M., Waterman D., Przyborowska A. M., Patel R. K., Fraser P. D., Bramley P. M.. 2005; Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS. J Exp Bot56:219–243 [CrossRef][PubMed]
    [Google Scholar]
  24. Hilgenberg W., Burke P. V., Sandmann G.. 1987; Metabolic pathways. In Phycomyces , pp.155–198 Edited by Cerdá-Olmedo E., Lipson E. D.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  25. Kanehisa M., Goto S., Hattori M., Aoki-Kinoshita K. F., Itoh M., Kawashima S., Katayama T., Araki M., Hirakawa M.. 2006; From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res34:D354–D357 [CrossRef][PubMed]
    [Google Scholar]
  26. Kuzina V., Cerdá-Olmedo E.. 2007; Ubiquinone and carotene production in the Mucorales Blakeslea and Phycomyces. Appl Microbiol Biotechnol76:991–999 [CrossRef][PubMed]
    [Google Scholar]
  27. Kuzina V., Domenech C., Cerdá-Olmedo E.. 2006; Relationships among the biosyntheses of ubiquinone, carotene, sterols, and triacylglycerols in Zygomycetes. Arch Microbiol186:485–493 [CrossRef][PubMed]
    [Google Scholar]
  28. Medina H. R.. 2013; Biosíntesis de apocarotenoides en Phycomyces blakesleeanus.
  29. Medina H. R., Cerdá-Olmedo E., Al-Babili S.. 2011; Cleavage oxygenases for the biosynthesis of trisporoids and other apocarotenoids in Phycomyces. Mol Microbiol82:199–208 [CrossRef][PubMed]
    [Google Scholar]
  30. Meissner G., Delbruck M.. 1968; Carotenes and retinal in Phycomyces mutants. Plant Physiol43:1279–1283 [CrossRef][PubMed]
    [Google Scholar]
  31. Murillo F. J., Cerdá-Olmedo E.. 1976; Regulation of carotene synthesis in Phycomyces. Mol Gen Genet148:19–24 [CrossRef][PubMed]
    [Google Scholar]
  32. Ootaki T., Lighty A. C., Delbrück M., Hsu W. J.. 1973; Complementation between mutants of Phycomyces deficient with respect to carotenogenesis. Mol Gen Genet121:57–70 [CrossRef][PubMed]
    [Google Scholar]
  33. Perez-Fons L., Bramley P. M., Fraser P. D.. 2014; The optimisation and application of a metabolite profiling procedure for the metabolic phenotyping of Bacillus species. Metabolomics10:77–90 [CrossRef]
    [Google Scholar]
  34. Riley G. J., Bramley P. M.. 1976; The subcellular distribution of carotenoids in Phycomyces blakesleeanus C115 car-42 mad-107(−). Biochim450:429–440 [CrossRef]
    [Google Scholar]
  35. Riley G. J., Bramley P. M.. 1982; Biosynthesis of carotenes in cell organelles of Phycomyces blakesleeanus C115 carS42 mad-107(−). Cytobios34:97–104
    [Google Scholar]
  36. Ruiz-Albert J., Cerdá-Olmedo E., Corrochano L. M.. 2002; Genes for mevalonate biosynthesis in Phycomyces. Mol Genet Genomics266:768–777 [CrossRef][PubMed]
    [Google Scholar]
  37. Sumner L. W., Amberg A., Barrett D., Beale M. H., Beger R., Daykin C. A., Fan T. W.-M., Fiehn O., Goodacre R. et al. 2007; Proposed minimum reporting standards for chemical analysis. Metabolomics3:211–221 [CrossRef]
    [Google Scholar]
  38. Sutter R. P.. 1975; Mutations affecting sexual development in Phycomyces blakesleeanus. Proc Natl Acad Sci USA72:127–130 [CrossRef][PubMed]
    [Google Scholar]
  39. Tagua V. G., Medina H. R., Martín-Domínguez R., Eslava A. P., Corrochano L. M., Cerdá-Olmedo E., Idnurm A.. 2012; A gene for carotene cleavage required for pheromone biosynthesis and carotene regulation in the fungus Phycomyces blakesleeanus. Fungal Genet Biol49:398–404 [CrossRef][PubMed]
    [Google Scholar]
  40. Torres-Martínez S., Murillo F. J., Cerdá-Olmedo E.. 1980; Genetics of lycopene cyclization and substrate transfer in beta-carotene biosynthesis in Phycomyces. Genet Res36:299–309 [CrossRef][PubMed]
    [Google Scholar]
  41. van den Berg R. A., Hoefsloot H. C., Westerhuis J. A., Smilde A. K., van der Werf M. J.. 2006; Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics7:142 [CrossRef][PubMed]
    [Google Scholar]
  42. Zalokar M.. 1969; Intracellular centrifugal separation of organelles in Phycomyces. J Cell Biol41:494–509[PubMed][CrossRef]
    [Google Scholar]
  43. Zaripheh S., Nara T. Y., Nakamura M. T., Erdman J. W.. 2006; Dietary lycopene downregulates carotenoid 15,15'-monooxygenase and PPAR-gamma in selected rat tissues. J Nutr136:932–938[PubMed]
    [Google Scholar]
  44. Zycha H., Siepmann R., Linnemann G.. 1969; Mucorales. Eine Beschreibung Aller Gattungen Und Arten Dieser Pilzgruppe, Von H. Zycha Und R. Siepmann. Mit Einem Beitrag Zur Gattung Mortierella Von G. Linnemann Lehre: J. Cramer;
    [Google Scholar]
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