Based on null mutant experiments of 6-phosphogluconate dehydrogenase (Gnd) (a key enzyme of the cyclic oxidation pathway), and methenyl H4MPT cyclohydrolase (CH) (participating in the direct oxidation of formaldehyde via H4MPT derivatives), Chistoserdova et al. have found that Gnd null mutants were not obtained, but CH null mutants were obtained. The experimental result suggests “that this pathway oxidation is essential for growth on methylotrophic substrates”, and that linear oxidation of formaldehyde via H4MPT derivatives is not required for growth. More specifically, “results confirm previous suggestions that the cyclic formaldehyde oxidation pathway plays a crucial role in C1 metabolism of M. flagellatus KT strain, most probably as the major energy-generating pathway.”