Microbial arene oxidation
Microbial arene oxidation (MAO) is when microbes use enzymes to convert aromatic compounds into more oxidized forms. The first step is usually an arene oxide, and the best-known MAO products for synthesis are cis-1,2-dihydroxycyclohexadienes, called dihydrodiols. This reaction also helps organisms break down arenes.
Key enzymes are bacterial dioxygenases. They can oxidize a wide range of arenes, but their substrate preferences are broad and not very strict. These enzymes often give very high enantiomeric purity (more than 90%), but the exact purity depends on the substrate. Some substrates, like 1,4-substituted benzenes, can yield diols with lower enantiomeric purity. To obtain the opposite (unnatural) enantiomer, enzymes usually need to be engineered.
In MAO, bacterial dioxygenases typically produce cis-dihydrodiols, while enzymes from mammals and fungi tend to give trans-dihydrodiols. The cis form, together with labeling studies, points to a fleeting intermediate called a dioxetane, though this intermediate has not been observed directly. Cis-1,2-dihydrocatechol is an important synthetic building block.
Examples of enzyme activity include:
- Toluene dioxygenase turning toluene into a dihydrodiol derivative.
- Aromatic esters being oxidized to dihydrodiols, with some other products.
- Naphthalene dioxygenase from Pseudomonas species acting on naphthalene and other polycyclic aromatics, though yields are usually lower for substrates other than naphthalene.
- Biphenyl dioxygenase oxidizing a broad set of aromatics with low substrate specificity; it can also be used with other dioxygenases.
A distinctive feature of some enzymes (BZDs) is ipso-cis oxidation, which does not follow the arene’s substitution pattern. Side products are common, especially with non-natural substrates, and benzylic oxidation can also occur.
A major limitation is that wild-type MAO typically produces only one enantiomer of the product. Creating enzymes that give the opposite enantiomer requires engineering, a focus of current research.
Because MAO can be slow or imprecise for complex substrates, it is usually used early in synthetic schemes. Simple dihydrodiols can be transformed into more complex products, and MAO tolerates many functional groups. For example, iodobenzene can be oxidized to iodo-containing dihydrodiols, which can then be elaborated into natural alkaloids. Some MAO work requires careful, aseptic handling of microbes and sometimes special strains. Dihydrodiols must be stored at basic pH (above 9) to prevent dehydration.
This page was last edited on 3 February 2026, at 20:50 (CET).