The growth rate-limiting reaction in methanol-assimilating yeasts

The maximum growth rate of methylotrophic yeasts during growth on methanol is about 0.2 h-1. Since they are able to grow faster on substrates such as glucose we tried to identify the putative limiting step in methanol metabolism within the assimilatory pathway, leading to the formation of a major precursor for biosyntheses, or within the linear dissimilatory sequence. Growth experiments with mixed substrates and determination of some kinetic parameters allowed us to restrict the number of possible pacemaker enzymes. The dissimilatory sequence does not seem to be growth-rate limiting. This also applies to transketolase, transaldolase and fructose-1,6-bisphosphatase. Surprisingly, methanol oxidase appears to be the prime candidate.