View source for Gibberellin biosynthesis

'''Gibberellin biosynthesis''' is a primary metabolic pathway that occurs in all higher plants but not, apparently, in other organisms. The main products are [[gibberellin]]s, functionalized [[diterpene]]s which have important [[Hormone|hormonal]] roles in processes from seed germination to stem growth to reproduction. A number of species also produce diterpenes based on the [[kaurane]] skeleton from the same biosynthetic pathway.

The pathway can be divided into two portions: the synthesis of [[Gibberellin A12|gibberellin A<sub>12</sub>]] from [[geranylgeranyl pyrophosphate]], and the functionalization of gibberellin A<sub>12</sub> into gibberellin hormones such as [[gibberellic acid]].

==Synthesis of the gibberellin skeleton==
The gibberellin skeleton, in the form of gibberellin A<sub>12</sub>, is synthesized from geranylgeranyl pyrophosphate in eight steps catalyzed by three different enzymes (although there are four distinct enzymic activities).

The first committed step in gibberellin and kaurane biosynthesis is the the partial cyclization of geranylgeranyl pyrophosphate to [[Copalyl pyrophosphate|''ent''-copalyl pyrophosphate]], catalyzed by [[Ent-Copalyl diphosphate synthase|''ent''-copalyl diphosphate synthase]] (EC&nbsp;5.5.1.12).<ref>{{citation | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC5/5/1/12.html | contribution = EC&nbsp;5.5.1.12 – ''ent''-copalyl diphosphate synthase | title = IUBMB Enzyme Nomenclature | accessdate = 2009-09-18}}.</ref> This reaction forms the opposite [[enantiomer]], (−)-copalyl pyrophosphate, from that used in other [[diterpene biosynthesis|diterpene biosyntheses]], isolating the production of gibberellin hormones from other metabolic pathways.

The cyclization process is completed by the transformation of ''ent''-copalyl pyrophosphate to [[Ent-Kaurene|''ent''-kaurene]], catalyzed by [[Ent-Kaurene synthase|''ent''-kaurene synthase]] (EC&nbsp;4.2.3.19).<ref>{{citation | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC4/2/3/19.html | contribution = EC&nbsp;4.2.3.19 – ''ent''-kaurene synthase | title = IUBMB Enzyme Nomenclature | accessdate = 2009-09-18}}.</ref> The formation of the two rings has been shown to proceed by a cyclization–rearrangement mechanism to produce the observed stereochemistry.<ref>{{citation | title = Stereochemistry of the Enzymic Cyclization of Copalyl Pyrophosphate to Kaurene in Enzyme Preparations from ''Marah macrocarpus'' | first1 = Robert M. | last1 = Coates | first2 = Patricia L. | last2 = Cavender | journal = J. Am. Chem. Soc. | year = 1980 | volume = 102 | issue = 20 | pages = 6358–59 | doi = 10.1021/ja00540a040}}.</ref>

In those cases which have been studied, ''ent''-copalyl diphosphate synthase and ''ent''-kaurene synthase activities are shown by the same protein, which is often simply referred to as kaurene synthase. It is a cytosolic enzyme widely distributed among different plant tissue types.

While some kaurane terpenes may be synthesized directly from ''ent''-kaurene, the next major step is the oxidation of ''ent''-kaurene to [[Ent-Kaurenoic acid|''ent''-kaurenoic acid]], catalyzed by a [[cytochrome P450]] enzyme, [[Ent-Kaurene oxidase|''ent''-kaurene oxidase]] (EC&nbsp;1.14.13.78),<ref>{{citation | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/14/13/78.html | contribution = EC&nbsp;1.14.13.78 – ''ent''-kaurene oxidase | title = IUBMB Enzyme Nomenclature | accessdate = 2009-09-05}}.</ref><ref>{{citation | title = Cloning of the ''Arabidopsisent''-kaurene oxidase gene GA3 | first1 = Chris A. | last1 = Helliwell | first2 = Candice C. | last2 = Sheldon | first3 = Mark R. | last3 = Olive | first4 = Amanda R. | last4 = Walker | first5 = Jan A. D. | last5 = Zeevaart | first6 = W. James | last6 = Peacock | first7 = Elizabeth S. | last7 = Dennis | journal = Proc. Natl. Acad. Sci. USA | year = 1998 | volume = 95 | issue = 15 | pages = 9019–24 | url = http://www.pnas.org/content/95/15/9019.full}}.</ref> bound to the outer [[chloroplast]]ic membrane.

Finally, ''ent''-kaurenoic acid is oxidized further to [[Gibberellin A12|gibberellin A<sub>12</sub>]], catalyzed by a second cytochrome P450 enzyme (from the CYP88A subfamily), [[Ent-Kaurenoic acid oxidase|''ent''-kaurenoic acid oxidase]] (EC&nbsp;1.14.13.79).<ref>{{citation | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/14/13/79.html | contribution = EC&nbsp;1.14.13.79 – ''ent''-kaurenoic acid oxidase | title = IUBMB Enzyme Nomenclature | accessdate = 2009-09-05}}.</ref><ref>{{citation | title = The CYP88A cytochrome P450, ''ent''-kaurenoic acid oxidase, catalyzes three steps of the gibberellin biosynthesis pathway | first1 = Chris A. | last1 = Helliwell | first2 = Peter M. | last2 = Chandler | first3 = Andrew | last3 = Poole | first4 =  Elizabeth S. | last4 = Dennis | first5 = W. James | last5 = Peacock | journal = Proc. Natl. Acad. Sci. USA | year = 2001 | volume = 98 | issue = 4 | pages = 2065–70 | url = http://www.pnas.org/content/98/4/2065.full}}.</ref>

==Bioactive gibberellins==
While it is believed that all [[gibberellin]]s are derived from giberellin A<sub>12</sub>, many of the details of the biosynthetic pathway have yet to be elucidated. One important step is the oxidative removal of carbon-20 in giberellin A<sub>12</sub>, catalyzed by [[gibberellin 20-oxidase]], a soluble 2-oxoglutarate-dependent [[dioxygenase]].<ref>{{citation | title = Expression cloning of a gibberellin 20-oxidase, a multifunctional enzyme involved in gibberellin biosynthesis | first1 = Theodor | last1 = Lange | first2 = Peter | last2 = Hedden | first3 = Jan E. | last3 = Graebe | journal = Proc. Natl. Acad. Sci. USA | year = 1994 | volume = 91 | issue = 18 | pages = 8552–56 | url = http://www.pnas.org/content/91/18/8552.full.pdf+html}}.</ref> Other relevant enzymes include [[gibberellin-44 dioxygenase]] (EC&nbsp;1.14.11.12), [[gibberellin 2β-dioxygenase]] (EC&nbsp;1.14.11.13) and [[gibberellin 3β-dioxygenase]] (EC&nbsp;1.14.11.15).

== References ==
{{reflist}}

== External links ==
*[http://www.genome.jp/kegg-bin/show_pathway?ec00904 Diterpenoid biosynthesis] from KEGG

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