Skip to main content
SpringerLink
Log in

The zinc cluster transcriptional regulator Asg1 transcriptionally coordinates oleate utilization and lipid accumulation in Saccharomyces cerevisiae

  • Applied microbial and cell physiology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

In this study, we characterize a new function for activator of stress response genes (Asg1) in fatty acid utilization. Asg1 is required for full activation of genes in several pathways, including β-oxidation (POX1, FOX2, and POT1), gluconeogenesis (PCK1), glyoxylate cycle (ICL1), triacylglycerol breakdown (TGL3), and peroxisomal transport (PXA1). In addition, the transcriptional activator Asg1 is found to be enriched on promoters of genes in β-oxidation and gluconeogenesis pathways, suggesting that Asg1 is directly involved in the control of fatty acid utilizing genes. In agreement, impaired growth on non-fermentable carbons such as fatty acids and oils and increased sensitivity to some oxidative agents are found for the Δasg1 strain. The lipid class profile of the Δasg1 cells grown in oleate displays approximately 3-fold increase in free fatty acid (FFA) content in comparison to glucose-grown cells, which correlates with decreased expression of β-oxidation genes. The ∆asg1 strain grown in glucose also exhibits higher accumulation of triacylglycerols (TAGs) during log phase, reaching levels typically observed in stationary phase cells. Altered TAG accumulation is partly due to the inability of the Δasg1 cells to efficiently break down TAGs, which is consistent with lowered expression of TGL3 gene, encoding triglycerol lipase. Overall, these results highlight a new role of the transcriptional regulator Asg1 in coordinating expression of genes involved in fatty acid utilization and its role in regulating cellular lipid accumulation, thereby providing an attractive approach to increase FFAs and TAGs content for the production of lipid-derived biofuels and chemicals in Saccharomyces cerevisiae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abramova NE, Cohen BD, Sertil O, Kapoor R, Davies KJA, Lowry CV (2001) Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae. Genetics 157(3):1169–1177

    CAS  PubMed  PubMed Central  Google Scholar 

  • Akache B, Wu K, Turcotte B (2001) Phenotypic analysis of genes encoding yeast zinc cluster proteins. Nucleic Acids Res 29(10):2181–2190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Athenstaedt K, Daum G (2003) YMR313c/TGL3 encodes a novel triacylglycerol lipase located in lipid particles of Saccharomyces cerevisiae. J Biol Chem 278(26):23317–23323

    Article  CAS  PubMed  Google Scholar 

  • Azocar L, Ciudad G, Heipieper HJ, Munoz R, Navia R (2010) Improving fatty acid methyl ester production yield in a lipase-catalyzed process using waste frying oils as feedstock. J Biosci Bioeng 109(6):609–614

    Article  CAS  PubMed  Google Scholar 

  • Baudin A, Ozier-Kalogeropoulos O, Denouel A, Lacroute F, Cullin C (1993) A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res 21(14):3329–3330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beopoulos A, Nicaud JM, Gaillardin C (2011) An overview of lipid metabolism in yeasts and its impact on biotechnological processes. Appl Microbiol Biotechnol 90(4):1193–1206

    Article  CAS  PubMed  Google Scholar 

  • Beopoulos A, Mrozova Z, Thevenieau F, Le Dall MT, Hapala I, Papanikolaou S, Chardot T, Nicaud JM (2008) Control of lipid accumulation in the yeast Yarrowia lipolytica. Appl Environ Microbiol 74(24):7779–7789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bourot S, Karst F (1995) Isolation and characterization of the Saccharomyces cerevisiae SUT1 gene involved in sterol uptake. Gene 165(1):97–102

    Article  CAS  PubMed  Google Scholar 

  • Cheirsilp B, Louhasakul Y (2013) Industrial wastes as a promising renewable source for production of microbial lipid and direct transesterification of the lipid into biodiesel. Bioresour Technol 142:329–337

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Zhang J, Chen WN (2014) Engineering the Saccharomyces cerevisiae β-oxidation pathway to increase medium chain fatty acid production as potential biofuel. PLoS One 9(1):e84853

    Article  PubMed  PubMed Central  Google Scholar 

  • Costa V, Moradas-Ferreira P (2001) Oxidative stress and signal transduction in Saccharomyces cerevisiae: insights into ageing, apoptosis and diseases. Mol Asp Med 22(4–5):217–246

    Article  CAS  Google Scholar 

  • Coste AT, Ramsdale M, Ischer F, Sanglard D (2008) Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae. Microbiology 154(Pt 5):1491–1501

    Article  CAS  PubMed  Google Scholar 

  • Czabany T, Athenstaedt K, Daum G (2007) Synthesis, storage and degradation of neutral lipids in yeast. Biochim Biophys Acta 1771(3):299–309

    Article  CAS  PubMed  Google Scholar 

  • Drolet J (2007) Evidence for the involvement of the zinc cluster protein Asg1p in the transcriptional regulation of some stress response genes in Saccharomyces cerevisiae. McGill University, Montreal, Canada

  • Dulermo T, Treton B, Beopoulos A, Kabran Gnankon AP, Haddouche R, Nicaud JM (2013) Characterization of the two intracellular lipases of Y. lipolytica encoded by TGL3 and TGL4 genes: new insights into the role of intracellular lipases and lipid body organisation. Biochim Biophys Acta 1831(9):1486–1495

    Article  CAS  PubMed  Google Scholar 

  • Dyer JM, Chapital DC, Kuan JW, Mullen RT, Pepperman AB (2002) Metabolic engineering of Saccharomyces cerevisiae for production of novel lipid compounds. Appl Microbiol Biotechnol 59(2–3):224–230

    CAS  PubMed  Google Scholar 

  • Erdmann R (1994) The peroxisomal targeting signal of 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae. Yeast 10(7):935–944

    Article  CAS  PubMed  Google Scholar 

  • Fernandez E, Moreno F, Rodicio R (1992) The ICL1 gene from Saccharomyces cerevisiae. Eur J Biochem 204(3):983–990

    Article  CAS  PubMed  Google Scholar 

  • Gurvitz A, Rottensteiner H (2006) The biochemistry of oleate induction: transcriptional upregulation and peroxisome proliferation. Biochim Biophys Acta 1763(12):1392–1402

    Article  CAS  PubMed  Google Scholar 

  • Gurvitz A, Wabnegger L, Rottensteiner H, Dawes IW, Hartig A, Ruis H, Hamilton B (2000) Adr1p-dependent regulation of the oleic acid-inducible yeast gene SPS19 encoding the peroxisomal β-oxidation auxiliary enzyme 2,4-dienoyl-CoA reductase. Mol Cell Biol Res Commun 4(2):81–89

    Article  CAS  PubMed  Google Scholar 

  • Gurvitz A, Hiltunen JK, Erdmann R, Hamilton B, Hartig A, Ruis H, Rottensteiner H (2001) Saccharomyces cerevisiae Adr1p governs fatty acid β-oxidation and peroxisome proliferation by regulating POX1 and PEX11. J Biol Chem 276(34):31825–31830

    Article  CAS  PubMed  Google Scholar 

  • Haddouche R, Poirier Y, Delessert S, Sabirova J, Pagot Y, Neuveglise C, Nicaud JM (2011) Engineering polyhydroxyalkanoate content and monomer composition in the oleaginous yeast Yarrowia lipolytica by modifying the β-oxidation multifunctional protein. Appl Microbiol Biotechnol 91(5):1327–1340

    Article  CAS  PubMed  Google Scholar 

  • Hartman JL, Garvik B, Hartwell L (2001) Cell biology—principles for the buffering of genetic variation. Science 291(5506):1001–1004

    Article  CAS  PubMed  Google Scholar 

  • Hatem E, Berthonaud V, Dardalhon M, Lagniel G, Baudouin-Cornu P, Huang M-E, Labarre J, Chédin S (2014) Glutathione is essential to preserve nuclear function and cell survival under oxidative stress. Free Radic Biol Med 67:103–114

    Article  CAS  PubMed  Google Scholar 

  • Hiltunen JK, Mursula AM, Rottensteiner H, Wierenga RK, Kastaniotis AJ, Gurvitz A (2003) The biochemistry of peroxisomal β-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 27(1):35–64

    Article  CAS  PubMed  Google Scholar 

  • Janssen HJ, Steinbüchel A (2014) Production of triacylglycerols in Escherichia coli by deletion of the diacylglycerol kinase gene and heterologous overexpression of atfA from Acinetobacter baylyi ADP1. Appl Microbiol Biotechnol 98(4):1913–1924

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen P, Nelson B, Robinson MD, Chen Y, Andrews B, Tyers M, Boone C (2002) High-resolution genetic mapping with ordered arrays of Saccharomyces cerevisiae deletion mutants. Genetics 162(3):1091–1099

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kamisaka Y, Noda N, Tomita N, Kimura K, Kodaki T, Hosaka K (2006) Identification of genes affecting lipid content using transposon mutagenesis in Saccharomyces cerevisiae. Biosci Biotechnol Biochem 70(3):646–653

    Article  CAS  PubMed  Google Scholar 

  • Karpichev IV, Small GM (1998) Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Mol Cell Biol 18(11):6560–6570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karpichev IV, Luo Y, Marians RC, Small GM (1997) A complex containing two transcription factors regulates peroxisome proliferation and the coordinate induction of β-oxidation enzymes in Saccharomyces cerevisiae. Mol Cell Biol 17(1):69–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch B, Schmidt C, Daum G (2014) Storage lipids of yeasts: a survey of nonpolar lipid metabolism in Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica. FEMS Microbiol Rev 38(5):892–915

    Article  CAS  PubMed  Google Scholar 

  • Kohlwein SD, Veenhuis M, van der Klei IJ (2013) Lipid droplets and peroxisomes: key players in cellular lipid homeostasis or a matter of fat—store 'em up or burn 'em down. Genetics 193(1):1–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunau WH, Hartig A (1992) Peroxisome biogenesis in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek 62(1–2):63–78

    Article  CAS  PubMed  Google Scholar 

  • Kurita O (2003) Overexpression of peroxisomal malate dehydrogenase MDH3 gene enhances cell death on H2O2 stress in the ald5 mutant of Saccharomyces cerevisiae. Curr Microbiol 47(3):192–197

    Article  CAS  PubMed  Google Scholar 

  • Larochelle M, Drouin S, Robert F, Turcotte B (2006) Oxidative stress-activated zinc cluster protein Stb5 has dual activator/repressor functions required for pentose phosphate pathway regulation and NADPH production. Mol Cell Biol 26(17):6690–6701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lennen RM, Pfleger BF (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr Opin Biotechnol 24(6):1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Li X, Guo D, Cheng Y, Zhu F, Deng Z, Liu T (2014) Overproduction of fatty acids in engineered Saccharomyces cerevisiae. Biotechnol Bioeng 111(9):1841–1852

    Article  CAS  PubMed  Google Scholar 

  • Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr., Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 100(6):3077–3082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔ C T method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  • Louhasakul Y, Cheirsilp B (2013) Industrial waste utilization for low-cost production of raw material oil through microbial fermentation. Appl Biochem Biotechnol 169(1):110–122

    Article  CAS  PubMed  Google Scholar 

  • MacPherson S, Larochelle M, Turcotte B (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minard KI, McAlister-Henn L (1991) Isolation, nucleotide sequence analysis, and disruption of the MDH2 gene from Saccharomyces cerevisiae: evidence for three isozymes of yeast malate dehydrogenase. Mol Cell Biol 11(1):370–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minard KI, McAlister-Henn L (1999) Dependence of peroxisomal β-oxidation on cytosolic sources of NADPH. J Biol Chem 274(6):3402–3406

    Article  CAS  PubMed  Google Scholar 

  • Ness F, Bourot S, Regnacq M, Spagnoli R, Berges T, Karst F (2001) SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells. Eur J Biochem 268(6):1585–1595

    Article  CAS  PubMed  Google Scholar 

  • Nielsen J, Jewett MC (2008) Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae. FEMS Yeast Res 8(1):122–131

    Article  CAS  PubMed  Google Scholar 

  • Papanikolaou S, Chevalot I, Komaitis M, Marc I, Aggelis G (2002) Single cell oil production by Yarrowia lipolytica growing on an industrial derivative of animal fat in batch cultures. Appl Microbiol Biotechnol 58(3):308–312

    Article  CAS  PubMed  Google Scholar 

  • Rottensteiner H, Kal AJ, Filipits M, Binder M, Hamilton B, Tabak HF, Ruis H (1996) Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae. EMBO 15(12):2924–2934

    CAS  Google Scholar 

  • Runguphan W, Keasling JD (2014) Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals. Metab Eng 21:103–113

    Article  CAS  PubMed  Google Scholar 

  • Sandager L, Gustavsson MH, Stahl U, Dahlqvist A, Wiberg E, Banas A, Lenman M, Ronne H, Stymne S (2002) Storage lipid synthesis is non-essential in yeast. J Biol Chem 277(8):6478–6482

    Article  CAS  PubMed  Google Scholar 

  • Scharnewski M, Pongdontri P, Mora G, Hoppert M, Fulda M (2008) Mutants of Saccharomyces cerevisiae deficient in acyl-CoA synthetases secrete fatty acids due to interrupted fatty acid recycling. FEBS J 275(11):2765–2778

    Article  CAS  PubMed  Google Scholar 

  • Schneider BL, Seufert W, Steiner B, Yang QH, Futcher AB (1995) Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae. Yeast 11(13):1265–1274

    Article  CAS  PubMed  Google Scholar 

  • Schüller HJ (2003) Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae. Curr Genet 43(3):139–160

    PubMed  Google Scholar 

  • Sikorski RS, Hieter P (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122(1):19–27

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sitepu IR, Garay LA, Sestric R, Levin D, Block DE, German JB, Boundy-Mills KL (2014) Oleaginous yeasts for biodiesel: current and future trends in biology and production. Biotechnol Adv 32(7):1336–1360

    Article  CAS  PubMed  Google Scholar 

  • Soontorngun N, Larochelle M, Drouin S, Robert F, Turcotte B (2007) Regulation of gluconeogenesis in Saccharomyces cerevisiae is mediated by activator and repressor function of Rds2. Mol Cell Biol 27(22):7895–7905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soontorngun N, Baramee S, Tangsombatvichit C, Thepnok P, Cheevadhanarak S, Robert F, Turcotte B (2012) Genome-wide location analysis reveals an important overlap between the targets of the yeast transcriptional regulators Rds2 and Adr1. Biochem Biophys Res Commun 423(4):632–637

    Article  CAS  PubMed  Google Scholar 

  • Sorger D, Daum G (2003) Triacylglycerol biosynthesis in yeast. Appl Microbiol Biotechnol 61(4):289–299

    Article  CAS  PubMed  Google Scholar 

  • Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18(2):321–336

    Article  CAS  PubMed  Google Scholar 

  • Tang X, Feng H, Chen WN (2013) Metabolic engineering for enhanced fatty acids synthesis in Saccharomyces cerevisiae. Metab Eng 16:95–102

    Article  CAS  PubMed  Google Scholar 

  • Tangsombatvichit P, Semkiv MV, Sibirny AA, Jensen LT, Ratanakhanokchai K, Soontorngun N (2015) Zinc cluster protein Znf1, a novel transcription factor of non-fermentative metabolism in Saccharomyces cerevisiae. FEMS Yeast Res 15(2):1–16

    Article  Google Scholar 

  • Thepnok P, Ratanakhanokchai K, Soontorngun N (2014) The novel zinc cluster regulator Tog1 plays important roles in oleate utilization and oxidative stress response in Saccharomyces cerevisiae. Biochem Biophys Res Commun 450(4):1276–1282

    Article  CAS  PubMed  Google Scholar 

  • Tong AH, Boone C (2006) Synthetic genetic array analysis in Saccharomyces cerevisiae. Methods Mol Biol 313:171–192

    CAS  PubMed  Google Scholar 

  • Turcotte B, Liang XB, Robert F, Soontorngun N (2010) Transcriptional regulation of nonfermentable carbon utilization in budding yeast. FEMS Yeast Res 10(1):2–13

    Article  CAS  PubMed  Google Scholar 

  • Valdes-Hevia MD, de la Guerra R, Gancedo C (1989) Isolation and characterization of the gene encoding phosphoenolpyruvate carboxykinase from Saccharomyces cerevisiae. FEBS Lett 258(2):313–316

    Article  CAS  PubMed  Google Scholar 

  • Veen M, Lang C (2004) Production of lipid compounds in the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 63(6):635–646

    Article  CAS  PubMed  Google Scholar 

  • Winston F, Dollard C, Ricupero-Hovasse SL (1995) Construction of a set of convenient Saccharomyces cerevisiae strains that are isogenic to S288C. Yeast 11(1):53–55

    Article  CAS  PubMed  Google Scholar 

  • Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich F, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M'Rabet N, Menard P, Mittmann M, Pai C, Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-MacDonald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK, Veronneau S, Voet M, Volckaert G, Ward TR, Wysocki R, Yen GS, Yu K, Zimmermann K, Philippsen P, Johnston M, Davis RW (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285(5429):901–906

    Article  CAS  PubMed  Google Scholar 

  • Zhou YJ, Buijs NA, Siewers V, Nielsen J (2014) Fatty acid-derived biofuels and chemicals production in Saccharomyces cerevisiae. Front Bioeng Biotechnol 2(32):1–6

    Google Scholar 

Download references

Acknowledgments

We would like to express our deepest gratitude to Drs. B. Turcotte (McGill University, Canada) and L.T. Jensen as well as C. Booncherd (Mahidol University, Thailand) for their generous gift of strains, pRS316 vector and some chemical reagents, K. Aryusuk, K. Poomputsa, N. Jeyashoke, S. Cheevathanarak, and K. Rattanakhanokchai (KMUTT, Thailand) for kind pieces of advice. We wish to acknowledge S. Watanachaisereekul, P. Thepnok, P. Tangsombatvichit, A. Poonsawad, and A. Siriatcharanon (KMUTT, Thailand) for technical assistance. We also express our sincere thanks to L.T. Jensen (Mahidol University, Thailand), L. Szmelc and C. Butler (KMUTT, Thailand) for critical reading of the manuscript.

This work is supported by a grant from the National Research Council of Thailand (NRCT) to NS and NRTC graduate studentship to SJ. We also thank KMUTT for providing facilities, travel grants and additional support.

Author information

Authors and Affiliations

  1. Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut’s University of Technology Thonburi, 49 Tianthalay Road, Tha Kham, Bangkhuntian, Bangkok, 10150, Thailand

    Siripat Jansuriyakul, Pichayada Somboon, Napachai Rodboon & Nitnipa Soontorngun

  2. NAS of Ukraine, Institute of Cell Biology, Drahomanov Street, 14/16, Lviv, 79005, Ukraine

    Olena Kurylenko & Andriy Sibirny

  3. Department of Bioetchnology and Microbiology, University of Rzeszow, Zelwerowicza Street, 4, 35-601, Rzeszow, Poland

    Andriy Sibirny

Authors
  1. Siripat Jansuriyakul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pichayada Somboon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Napachai Rodboon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olena Kurylenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andriy Sibirny
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nitnipa Soontorngun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nitnipa Soontorngun.

Ethics declarations

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jansuriyakul, S., Somboon, P., Rodboon, N. et al. The zinc cluster transcriptional regulator Asg1 transcriptionally coordinates oleate utilization and lipid accumulation in Saccharomyces cerevisiae . Appl Microbiol Biotechnol 100, 4549–4560 (2016). https://doi.org/10.1007/s00253-016-7356-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-016-7356-4

Keywords

Search

Navigation