In this good quality paper where we report study of the enzyme complex (pathway) involved in the formation of allyl and methylmalonyl pathway. These are building blocks activated by AT4 domain from FK506 PKS complex encoding medically important immunosuppression drug, which is central part of this ARRS funded project. We demonstrated that the crotonyl CoA-reductase (CCR) is a central enzyme in this pathway. We have identified a second homologue, located in the ethylmalonyl-CoA pathway (EMC). We have demonstrated that these two CCR homologues do not interact, although their homology on the DNA and amino acid level is very high. Their activities are separated by different timimg of expression in the natural strain of S. tsukubaensis. In addition, their expression is dependent on the source of carbon. Interestingly, while in EMC pathway metabolites are CoA-activates, in the FK506 gene cluster allylmalonate is ACP activated, which directly impact the work current ARRS funded study. This paper brings very important understanding on the FK506 regulation and production of FK506-related impurities of high commercial importance.
COBISS.SI-ID: 4572536