We measure the radial profile of the 12CO(1-0) to H_2 conversion factor (Xco) in NGC 628. The Halpha emission from the VENGA integral field spectroscopy is used to map the star formation rate surface density (Sigma_{SFR}). We estimate the molecular gas surface density (Sigma_{H2}) from Sigma_{SFR} by inverting the molecular star formation law (SFL), and compare it to the CO intensity to measure Xco. We study the impact of systematic uncertainties by changing the slope of the SFL, using different SFR tracers (Halpha vs. far-UV plus 24mu m), and CO maps from different telescopes (single-dish and interferometers). The observed Xco profile is robust against these systematics, drops by a factor of 2 from R~7 kpc to the center of the galaxy, and is well fit by a gradient Delta log(Xco)=0.06pm0.02 dex kpc^-1. We study how changes in Xco follow changes in metallicity, gas density, and ionization parameter. Theoretical models show that the gradient in Xco can be explained by a combination of decreasing metallicity, and decreasing Sigma_{H2} with radius. Photoelectric heating from the local UV radiation field appears to contribute to the decrease of Xco in higher density regions. Our results show that galactic environment plays an important role at setting the physical conditions in star forming regions, in particular the chemistry of carbon in molecular complexes, and the radiative transfer of CO emission. We caution against adopting a single Xco value when large changes in gas surface density or metallicity are present.
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