Work on painting initially, American (4)
I believe the answer is:
opus
'work' is the definition.
(an opus is an artistic work)
'on painting initially american' is the wordplay.
'initially' says to take the initial letters.
'american' becomes 'US' (abbreviation for United States).
The initial letters of 'on painting' is 'op'.
'op'+'us'='OPUS'
(Other definitions for opus that I've seen before include "Composer's work" , "Showing creative skill" , "Musical composition in the soup" , "Major work" , "Composer's catalogue number" .)