Modifying the namespace mapping of a node is not possible in lxml. See this open ticket that has this feature as a wishlist item.
It originated from this thread on the lxml mailing list, where a workaround replacing the root node is given as an alternative. There are some issues with replacing the root node though: see the ticket above.
I’ll put the suggested root replacement workaround code here for completeness:
>>> DOC = """<sbml xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" level="2" version="4">
... <model metaid="untitled" id="untitled">
... <annotation>...</annotation>
... <listOfUnitDefinitions>...</listOfUnitDefinitions>
... <listOfCompartments>...</listOfCompartments>
... <listOfSpecies>
... <species metaid="s1" id="s1" name="GenA" compartment="default" initialAmount="0">
... <annotation>
... <celldesigner:extension>...</celldesigner:extension>
... </annotation>
... </species>
... <species metaid="s2" id="s2" name="s2" compartment="default" initialAmount="0">
... <annotation>
... <celldesigner:extension>...</celldesigner:extension>
... </annotation>
... </species>
... </listOfSpecies>
... <listOfReactions>...</listOfReactions>
... </model>
... </sbml>"""
>>>
>>> from lxml import etree
>>> from StringIO import StringIO
>>> NS = "http://this.is.some/custom_namespace"
>>> tree = etree.ElementTree(element=None, file=StringIO(DOC))
>>> root = tree.getroot()
>>> nsmap = root.nsmap
>>> nsmap['kjw'] = NS
>>> new_root = etree.Element(root.tag, nsmap=nsmap)
>>> new_root[:] = root[:]
>>> new_root.append(etree.Element('{%s}%s' % (NS, 'test')))
>>> new_root.append(etree.Element('{%s}%s' % (NS, 'test')))
>>> print etree.tostring(new_root, pretty_print=True)
<sbml xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:kjw="http://this.is.some/custom_namespace" xmlns="http://www.sbml.org/sbml/level2/version4"><model metaid="untitled" id="untitled">
<annotation>...</annotation>
<listOfUnitDefinitions>...</listOfUnitDefinitions>
<listOfCompartments>...</listOfCompartments>
<listOfSpecies>
<species metaid="s1" id="s1" name="GenA" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>...</celldesigner:extension>
</annotation>
</species>
<species metaid="s2" id="s2" name="s2" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>...</celldesigner:extension>
</annotation>
</species>
</listOfSpecies>
<listOfReactions>...</listOfReactions>
</model>
<kjw:test/><kjw:test/></sbml>