Page 215 - Advances in Textile Biotechnology

196 Advances in textile biotechnology

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genomic level. All require the binding of Ca for their activity. In general,

mammal TGases display strict specificity in the recognition of glutamine

protein substrates and lower specificity for the acyl acceptor amine group,
which can either be the ε-amino group of peptidyl Lys or a low molecular
mass primary amine. Ohtsuka et al. (2000) reported some differences in the
substrate specificity of two TGases, one from guinea pig liver and one from

Streptomyces mobaraensis. Accordingly, differences in the structure of the
catalytic site between mammal and microbial TGases have been reported
(Lorand and Graham, 2003). These features, together with the fact that
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microbial TGases are totally Ca independent, confi rm the high heteroge-
neity of this family of enzymes.
TGases are present in most animal tissues and body fl uids (Griffi n et al.,
2002; Lorand and Graham, 2003). These enzymes play a key role in physiol-
ogy and development being involved in bone remodelling and ossifi cation,
skin maturation and integrity, development of heart, lung, salivary gland,
and central and peripheral nervous system, hematopoiesis, spermatogenesis,
egg-envelope formation following fertilisation, myofi brillogenesis, blood
coagulation, and programmed cell death (apoptosis) (Della Mea et al., 2007;
Ientile et al., 2007; Vanhoutte and Heymans, 2008; Bakker et al., 2008). One
member of the TGase family (TGase 3) is involved in the progressive scaf-

folding of hair shaft through specific formation of isopeptide bonds between
intermediate filaments and keratin-associated proteins (Thibaut et al.,

2009). In general, the reactions catalysed by TGases endow the resulting
supramolecular structure with extra rigidity and resistance against proteo-
lytic degradation. Having knowledge of these enzymes is also essential for
understanding the aetiologies of diverse hereditary diseases of blood and
skin, and various autoimmune, inflammatory and degenerative conditions,

a growing area of intensive TGase research (De Vivo and Gentile, 2008; De
Vivo et al., 2008). The fact that TGase activity increases in various infl am-

matory and fibrotic conditions, such as rheumatoid arthritis, liver, renal and

pulmonary fibrosis, erosive gastritis, leads to its implication in the patho-
genesis of these disorders. Noteworthy, TGase activity is increased and/or
crosslink formation is enhanced in all forms of mucosal infl ammation
(Crohn’s disease, ulcerative colitis, coeliac disease) and in mucosal epithe-
lial lesions, as well as in fibrotic disorders (Stenberg et al., 2008; Wieser and

Koehler, 2008). Last, but not least, TGases have been implicated in axonal
growth and regeneration, as well as in various degenerative neurological
diseases (for example: Huntington’s, Alzheimer’s, Parkinson’s and progres-
sive suprabulbar palsy) which are characterised by the abnormal accumula-
tion of insoluble protein aggregates that cause progressive neuronal death
(Wang et al., 2008).
The limited supply and the relatively high price have hindered for years
the industrial utilisation of tissue TGases, commonly extracted from guinea
pig liver, until the mass production of a microbial TGase from Streptomyces

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