Open Access Open Access  Restricted Access Subscription or Fee Access

Chitin synthase gene regulation in fungal species-An Insight

Kritika Gupta, Akshita Angirishi, Ratnesh Jain, Prajakta Dandekar

Abstract


Chitin synthase (CHS) gene is imperative for the formation of chitin, a polymer of N-acetyl glucosamine units. Chitin is an important component of the fungal cell wall, wherein it maintains the cell morphology and is involved in immune response of the host plants. Chitin synthases are classified according to the genes responsible of their production and their diverse functions in different fungi. Chitin production, which majorly occurs in insects and fungi, can thus be regulated by controlling the transcription and translation of the chitin synthase gene. Chitin is deacylated to form chitosan, which is a more soluble and flexible polymer that has been explored for diverse industrial applications. The CHS gene performs different functions at specific stages of cell cycle and is regulated by various factors that affect chitin production. CHS gene can be regulated using chitin inhibitors and thus acts as a suitable target for therapeutic molecules against various fungal diseases. In this manuscript we have discussed the regulation of CHS gene via chitin inhibitors and its implications on the chitin synthesis pathway. Further, the role of this pathway in various in vitro antifungal studies and therapeutic applications has been elaborately discussed.


Full Text:

PDF

References


Roncero, C. (2002). “The genetic complexity of chitin synthesis in fungi.” Current genetics 41(6): 367–378.

Merzendorfer, H. (2011). “The cellular basis of chitin synthesis in fungi and insects: common principles and differences.” European journal of cell biology 90(9): 759–769.

Cabib, E. (1981). Chitin: structure, metabolism, and regulation of biosynthesis. Plant Carbohydrates II, Springer: 395–415.

Lenardon, M.D., C.A. Munro, et al. (2010). “Chitin synthesis and fungal pathogenesis.” Current Opinion in Microbiology 13(4): 416–423.

Zhang J, Jiang H, Du Y, Keyhani NO, Xia Y, Jin K. Members of chitin synthase family in Metarhizium acridum differentially affect fungal growth, stress tolerances, cell wall integrity and virulence. PLoS pathogens. 2019 Aug 28;15(8):e1007964.

Cabib, E., R. Roberts, et al. (1982). “Synthesis of the yeast cell wall and its regulation.” Annual review of biochemistry 51(1): 763–793.

Rogg, L.E., J.R. Fortwendel, et al. (2012). “Regulation of expression, activity and localization of fungal chitin synthases.” Medical Mycology 50(1): 2–17.

Liu R, Xu C, Zhang Q, Wang S, Fang W. Evolution of the chitin synthase gene family correlates with fungal morphogenesis and adaption to ecological niches. Scientific reports. 2017 Mar 16;7(1):1–2.

Wang, Q., H. Liu, et al. (2002). “Compensatory expression of five chitin synthase genes, a response to stress stimuli, in Wangiella (Exophiala) dermatitidis, a melanized fungal pathogen of humans.” Microbiology 148(9): 2811–2817.

Munro, C., D. Schofield, et al. (1998). “Regulation of chitin synthesis during dimorphic growth of Candida albicans.” Microbiology 144(2): 391–401.

Lee, J.I., Y.M. Yu, et al. (2005). “Differential expression of the chsE gene encoding a chitin synthase of Aspergillus nidulans in response to developmental status and growth conditions.” FEMS Microbiology Letters 249(1): 121–129.

Bulawa, C.E., M. Slater, et al. (1986). “The S. cerevisiae structural gene for chitin synthase is not required for chitin synthesis in vivo.” Cell 46(2): 213–225.

Cabib, E., A. Sburlati, et al. (1989). "Chitin synthase 1, an auxiliary enzyme for chitin synthesis in Saccharomyces cerevisiae." The Journal of cell biology 108(5): 1665-1672.

Munro, C.A. and N.A. Gow (2001). “Chitin synthesis in human pathogenic fungi.” Med Mycol 1: 41–53.

Ichinomiya, M., H. Horiuchi, et al. (2002). “Different functions of the class I and class II chitin synthase genes, chsC and chsA, are revealed by repression of chsB expression in Aspergillus nidulans.” Current genetics 42(1): 51–58.

Sburlati, A. and E. Cabib (1986). “Chitin synthetase 2, a presumptive participant in septum formation in Saccharomyces cerevisiae.” Journal of Biological Chemistry 261(32): 15147–15152.

Shaw, J.A., P.C. Mol, et al. (1991). “The function of chitin synthases 2 and 3 in the Saccharomyces cerevisiae cell cycle.” Journal of Cell Biology 114(1): 111–123.

Silverman, S.J. (1989). “Similar and different domains of chitin synthases 1 and 2 of S. cerevisiae: two isozymes with distinct functions.” Yeast 5(6): 459–467.

Xoconostle-Cázares, B., C.A. Specht, et al. (1997). “Umchs5, a gene coding for a class IV chitin synthase in Ustilago maydis.” Fungal Genet Biol 22(3): 199–208.

Horiuchi, H., M. Fujiwara, et al. (1999). “Proliferation of intrahyphal hyphae caused by disruption of csmA, which encodes a class V chitin synthase with a myosin motor-like domain in Aspergillus nidulans.” Journal of bacteriology 181(12): 3721–3729.

Mellado, E., C.A. Specht, et al. (1996). “Cloning and characterization of chsD, a chitin synthase-like gene of Aspergillus fumigatus.” FEMS Microbiology Letters 143(1): 69–76.

Specht, C.A., Y. Liu, et al. (1996). “The chsD and chsE genes of Aspergillus nidulans and their roles in chitin synthesis.” Fungal Genet Biol 20(2): 153–167.

Sánchez N, Roncero C. Chitin Synthesis in Yeast: A Matter of Trafficking. International Journal of Molecular Sciences. 2022 Oct 14;23(20):12251.

Din, A.B., C.A. Specht, et al. (1996). “chs-4, a class IV chitin synthase gene fromNeurospora crassa.” Molecular and General Genetics MGG 250(2): 214–222.

Aufauvre-Brown, A., E. Mellado, et al. (1997). “Aspergillus fumigatus chsE: A Gene Related toCHS3ofSaccharomyces cerevisiaeand Important for Hyphal Growth and Conidiophore Development but Not Pathogenicity.” Fungal Genetics and Biology 21(1): 141–152.

Morcx, S., C. Kunz, et al. (2013). “Disruption of Bcchs4, Bcchs6 or Bcchs7 chitin synthase genes in Botrytis cinerea and the essential role of class VI chitin synthase (Bcchs6).” Fungal Genetics and Biology 52: 1–8.

Takeshita, N., S. Yamashita, et al. (2006). “Aspergillus nidulans class V and VI chitin synthases CsmA and CsmB, each with a myosin motor‐like domain, perform compensatory functions that are essential for hyphal tip growth.” Molecular microbiology 59(5): 1380–1394.

Martín-Urdíroz, M., M.I.G. Roncero, et al. (2008). “ChsVb, a class VII chitin synthase involved in septation, is critical for pathogenicity in Fusarium oxysporum.” Eukaryotic cell 7(1): 112–121.

Cabib, E., S.J. Silverman, et al. (1992). “Chitinase and chitin synthase 1: counterbalancing activities in cell separation of Saccharomyces cerevisiae.” Microbiology 138(1): 97–102.

Silverman, S.J., A. Sburlati, et al. (1988). “Chitin synthase 2 is essential for septum formation and cell division in Saccharomyces cerevisiae.” Proceedings of the National Academy of Sciences of the United States of America 85(13): 4735–4739.

Valdivieso, M.H., P.C. Mol, et al. (1991). “CAL1, a gene required for activity of chitin synthase 3 in Saccharomyces cerevisiae.” The Journal of cell biology 114(1): 101–109.

Gow, N., P. Robbins, et al. (1994). “A hyphal-specific chitin synthase gene (CHS2) is not essential for growth, dimorphism, or virulence of Candida albicans.” Proceedings of the National Academy of Sciences 91(13): 6216–6220.

Fujiwara, M., M. Ichinomiya, et al. (2000). “Evidence that the Aspergillus nidulans class I and class II chitin synthase genes, chsC and chsA, share critical roles in hyphal wall integrity and conidiophore development.” The Journal of Biochemistry 127(3): 359–366.

Choi, W.-J. and E. Cabib (1994). “The use of divalent cations and pH for the determination of specific yeast chitin synthetases.” Analytical biochemistry 219(2): 368–372.

Schmidt, M., B. Bowers, et al. (2002). “In budding yeast, contraction of the actomyosin ring and formation of the primary septum at cytokinesis depend on each other.” Journal of cell science 115(2): 293–302.

Chuang, J.S. and R.W. Schekman (1996). “Differential trafficking and timed localization of two chitin synthase proteins, Chs2p and Chs3p.” The Journal of cell biology 135(3): 597–610.

Bulawa, C.E. and B.C. Osmond (1990). “Chitin synthase I and chitin synthase II are not required for chitin synthesis in vivo in Saccharomyces cerevisiae.” Proceedings of the National Academy of Sciences 87(19): 7424–7428.

Valdivieso, M.-H., Á. Durán, et al. (2004). Chitin Biosynthesis and Morphogenetic Processes. Biochemistry and Molecular Biology. R. Brambl and G. A. Marzluf. Berlin, Heidelberg, Springer Berlin Heidelberg: 275–290.

Santos, B., A. Duran, et al. (1997). “CHS5, a gene involved in chitin synthesis and mating in Saccharomyces cerevisiae.” Molecular and Cellular Biology 17(5): 2485–2496.

Trilla, J.A., T. Cos, et al. (1997). “Characterization of CHS4 (CAL2), a gene of Saccharomyces cerevisiae involved in chitin biosynthesis and allelic to SKT5 and CSD4.” Yeast 13(9): 795–807.

Chen‐Wu, J., J. Zwicker, et al. (1992). “Expression of chitin synthase genes during yeast and hyphal growth phases of Candida albicans.” Molecular microbiology 6(4): 497–502.

Côte, P., H. Hogues, et al. (2009). “Transcriptional analysis of the Candida albicans cell cycle.” Molecular biology of the cell 20(14): 3363–3373.

Spellman, P.T., G. Sherlock, et al. (1998). “Comprehensive identification of cell cycle–regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.” Molecular biology of the cell 9(12): 3273–3297.

Choi, W.J., B. Santos, et al. (1994). “Are yeast chitin synthases regulated at the transcriptional or the posttranslational level?” Molecular and Cellular Biology 14(12): 7685–7694.

Pammer, M., P. Briza, et al. (1992). “DIT101 (CSD2, CAL1), a cell cycle-regulated yeast gene required for synthesis of chitin in cell walls and chitosan in spore walls.” Yeast (Chichester, England) 8(12): 1089–1099.

Fonzi, W.A. (1999). “PHR1 and PHR2 of Candida albicans encode putative glycosidases required for proper cross-linking of beta-1,3- and beta-1,6-glucans.” Journal of bacteriology 181(22): 7070–7079.

Kapteyn, J. C., L. L. Hoyer, et al. (2000). “The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants.” Molecular microbiology 35(3): 601–611.

Popolo, L., D. Gilardelli, et al. (1997). “Increase in chitin as an essential response to defects in assembly of cell wall polymers in the ggp1delta mutant of Saccharomyces cerevisiae.” Journal of bacteriology 179(2): 463–469.

Becker, A., P. Schlöder, et al. (1996). “The regulation of trehalose metabolism in insects.” Experientia 52(5): 433–439.

François, J. and J.L. Parrou (2001). “Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae.” Fems microbiology reviews 25(1): 125–145.

ELORZA, M.V., H. RICO, et al. (1983). “Calcofluor white alters the assembly of chitin fibrils in Saccharomyces cerevisiae and Candida albicans cells.” Microbiology 129(5): 1577–1582.

Deng MD, McMullin T, Grund A, inventors; Arkion Life Sciences LLC, assignee. Metabolic engineering for enhanced production of chitin and chitosan in microorganisms. United States patent application US 10/823,397. 2005 Feb 24.

Orlean, P. (1997). “Biogenesis of yeast wall, surface components.” The molecular and cellular biology of the yeast Saccharomyces: 229–362.

Gooday, G.W. and D.A. Schofield (1995). “Regulation of chitin synthesis during growth of fungal hyphae: the possible participation of membrane stress.” Canadian journal of botany 73(S1): 114–121.

Martinez-Cadena, G. and J. Ruiz-Herrera (1987). “Activation of chitin synthetase from Phycomyces blakesleeanus by calcium and calmodulin.” Archives of microbiology 148(4): 280–285.

Bulawa, C.E. (1992). “CSD2, CSD3, and CSD4, genes required for chitin synthesis in Saccharomyces cerevisiae: the CSD2 gene product is related to chitin synthases and to developmentally regulated proteins in Rhizobium species and Xenopus laevis.” Molecular and Cellular Biology 12(4): 1764–1776.

Douglas, L.M., F.J. Alvarez, et al. (2005). “Septin function in yeast model systems and pathogenic fungi.” Eukaryotic cell 4(9): 1503–1512.

Lippincott, J. and R. Li (1998). “Sequential assembly of myosin II, an IQGAP-like protein, and filamentous actin to a ring structure involved in budding yeast cytokinesis.” The Journal of cell biology 140(2): 355–366.

Lesage, G. and H. Bussey (2006). “Cell wall assembly in Saccharomyces cerevisiae.” Microbiology and molecular biology reviews 70(2): 317–343.

DeMarini, D.J., A.E. Adams, et al. (1997). “A septin-based hierarchy of proteins required for localized deposition of chitin in the Saccharomyces cerevisiae cell wall.” The Journal of cell biology 139(1): 75–93.

Jiang C, Wang H, Liu M, Wang L, Yang R, Wang P, Lu Z, Zhou Y, Zheng Z, Zhao G. Identification of chitin synthase activator in Aspergillus niger and its application in citric acid fermentation. Applied Microbiology and Biotechnology. 2022 Nov;106(21):6993–7011.

Santos, B. and M. Snyder (1997). “Targeting of chitin synthase 3 to polarized growth sites in yeast requires Chs5p and Myo2p.” The Journal of cell biology 136(1): 95–110.

Valdivia, R.H. and R. Schekman (2003). “The yeasts Rho1p and Pkc1p regulate the transport of chitin synthase III (Chs3p) from internal stores to the plasma membrane.” Proceedings of the National Academy of Sciences 100(18): 10287–10292.

Reyes, A., M. Sanz, et al. (2007). “Chitin synthase III requires Chs4p-dependent translocation of Chs3p into the plasma membrane.” Journal of cell science 120(12): 1998–2009.

Sanz, M., O.A. Trilla, et al. (2002). “Control of chitin synthesis through Shc1p, a functional homologue of Chs4p specifically induced during sporulation.” Molecular microbiology 43(5): 1183–1195.

Iwamoto, M.A., S.R. Fairclough, et al. (2005). “Saccharomyces cerevisiae Sps1p regulates trafficking of enzymes required for spore wall synthesis.” Eukaryotic cell 4(3): 536–544.

Zhang, G., R. Kashimshetty, et al. (2006). “Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother–daughter neck via the secretory pathway in budding yeast.” The Journal of cell biology 174(2): 207–220.

Christodoulidou, A., V. Bouriotis, et al. (1996). “Two sporulation-specific chitin deacetylase-encoding genes are required for the ascospore wall rigidity of Saccharomyces cerevisiae.” Journal of Biological Chemistry 271(49): 31420–31425.

MISHRA, C., C.E. SEMINO, et al. (1997). “Cloning and expression of two chitin deacetylase genes of Saccharomyces cerevisiae.” Yeast 13(4): 327–336.

Saxena, I.M., R.M. Brown, Jr., et al. (1995). “Multidomain architecture of beta-glycosyl transferases: implications for mechanism of action.” Journal of bacteriology 177(6): 1419–1424.

M Chaudhary, P., S.G Tupe, et al. (2013). “Chitin synthase inhibitors as antifungal agents.” Mini reviews in medicinal chemistry 13(2): 222–236.

Isono, K., J. Nagatsu, et al. (1967). “Studies on polyoxins, antifungal antibiotics: Part V. Isolation and characterization of polyoxins C, D, E, F, G, H and I.” Agricultural and Biological Chemistry 31(2): 190–199.

Azuma, T., T. Saita, et al. (1977). “Polyoxin Analogs. III. Synthesis and Biological Activity of Aminoacyl Derivatives of Polyoxins C and L.” Chemical & Pharmaceutical Bulletin 25(7): 1740–1748.

Masubuchi, K., M. Taniguchi, et al. (2000). “Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors.” Bioorganic & Medicinal Chemistry Letters 10(13): 1459–1462.

Bowers, B., G. Levin, et al. (1974). “Effect of Polyoxin D on Chitin Synthesis and Septum Formation in Saccharomyces cerevisiae.” Journal of bacteriology 119: 564–575.

Shenbagamurthi, P., H.A. Smith, et al. (1983). “Design of anticandidal agents: synthesis and biological properties of analogues of polyoxin L.” Journal of medicinal chemistry 26(10): 1518–1522.

Smith, H.A., P. Shenbagamurthi, et al. (1986). “Hydrophobic polyoxins are resistant to intracellular degradation in Candida albicans.” Antimicrobial agents and chemotherapy 29(1): 33–39.

Dähn, U., H. Hagenmaier, et al. (1976). “Stoffwechselprodukte von mikroorganismen. 154. Mitteilung. Nikkomycin, ein neuer hemmstoff der chitinsynthese bei pilzen.” Arch Microbiol 107(2): 143–160.

Bago, B., H. Chamberland, et al. (1996). “Effect of Nikkomycin Z, a chitin-synthase inhibitor, on hyphal growth and cell wall structure of two arbuscular-mycorrhizal fungi.” Protoplasma 192(1–2): 80–92.

Obi, K., J.-i. Uda, et al. (2000). “Novel nikkomycin analogues: inhibitors of the fungal cell wall biosynthesis enzyme chitin synthase.” Bioorganic & medicinal chemistry letters 10(13): 1451–1454.

Gaughran, J.P., M.H. Lai, et al. (1994). “Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo.” Journal of bacteriology 176(18): 5857–5860.

Chaudhary, P. M., S.R. Chavan, et al. (2009). “Exploration of click reaction for the synthesis of modified nucleosides as chitin synthase inhibitors.” Bioorganic & medicinal chemistry 17(6): 2433–2440.

DE ROUSSET-HALL, A. and G. Gooday (1975). “A kinetic study of a solubilized chitin synthetase preparation from Coprinus cinereus.” Microbiology 89(1): 146–154.

Cohen, E. and J.E. Casida (1980). “Inhibition of Tribolium gut chitin synthetase.” Pesticide Biochemistry and Physiology 13(2): 129–136.

Yeager, A.R. and N.S. Finney (2004). “The first direct evaluation of the two-active site mechanism for chitin synthase.” The Journal of Organic Chemistry 69(3): 613–618.

Yeager, A.R. and N.S. Finney (2004). “Second-generation dimeric inhibitors of chitin synthase.” Bioorganic & medicinal chemistry 12(24): 6451–6460.

Ge, Z., Q. Ji, et al. (2016). “Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents.” Journal of enzyme inhibition and medicinal chemistry 31(2): 219–228.

Bang, K.H., D.W. Lee, et al. (2000). “Inhibition of fungal cell wall synthesizing enzymes by trans-cinnamaldehyde.” Bioscience, biotechnology, and biochemistry 64(5): 1061–1063.

Sudoh, M., T. Yamazaki, et al. (2000). “Identification of a novel inhibitor specific to the fungal chitin synthase - Inhibition of chitin synthase 1 arrests the cell growth, but inhibition of chitin synthase 1 and 2 is lethal in the pathogenic fungus Candida albicans.” The Journal of biological chemistry 275: 32901–32905.


Refbacks

  • There are currently no refbacks.