Acetone and acetophenone are common intermediates of natural secondary metabolism. As these substrates are chemically inert, they must be activated prior to microbial degradation. In the known metabolic pathways, ketone activation proceeds either by oxygenation or by ATP-dependent carboxylation [1,2].

Acetone carboxylase (Acx) and acetophenone carboxylase (Apc) are homologous enzymes, but have different subunit compositions. While Acx forms a hexameric complex out of three different types of subunits ([αβγ]₂), the octameric Apc core complex comprises four distinct subunits ([αα′βγ]₂). Furthermore, Apc activity requires a fifth subunit (Apcε), which is not present in Acx [2,3].

The strictly aerobic actinobacterium Rhodococcus aetherivorans encodes an apparent apc operon. Surprisingly, acetone rather than acetophenone induces expression of this gene cluster. In contrast, a phenol monooxygenase homolog is up-regulated during growth on acetophenone. Under both conditions, we observe strong expression of isocitrate lyase, which is involved in acetyl-CoA assimilation.

Our current data suggest that acetone and acetophenone degradation in R. aetherivorans is accomplished by different principles. We propose that acetone catabolism is initiated by a carboxylase with Apc-like subunit structure and then proceeds in the canonical pathway via acetoacetate and acetyl-CoA. In contrast, acetophenone may be activated by oxygenation. The responsible enzyme and the subsequent reaction steps are not known yet, but we hypothesize that phenol and acetate are intermediates of the acetophenone degradation pathway.

[1] Heider et al., J Mol Microbiol Biotechnol 26:152-64 (2016).

[2] Weidenweber et al., Sci Rep 7:39674 (2017).

[3] Mus et al., Sci Rep 7:7234 (2017).