No abstract

The use of cytochromes P450 for the regio- and stereoselective hydroxylation of non-activated carbon atoms in biotechnological applications reflects an efficient and cost-effective alternative in comparison to classical organic chemistry. The prokaryotic cytochrome P450 CYP106A2 from Bacillus megaterium ATCC 13368 hydroxylates a variety of 3-oxo-Δ⁴ steroids and recently it was identified to carry out a one-step regioselective allylic hydroxylation of the diterpene abietic acid. The anti-inflammatory pentacyclic triterpene 11-keto-β-boswellic acid (KBA) was found to be a further substrate of CYP106A2, being the first report of a pentacyclic triterpene conversion by a prokaryotic P450. The reaction products were analyzed by HPLC and the corresponding kinetic parameters were investigated. Structure determination of the main product by NMR revealed a 15α-hydroxylation of this substrate. In order to overcome the inability of a recombinant P450 whole-cell system in E. coli for the uptake of acids with terpene structure, we developed for the first time an expression system for cytochromes P450 in B. megaterium (strains MS941 and ATCC 13368). Interestingly, CYP106A2 was only successfully expressed in the plasmid-less B. megaterium strain MS941 but not in ATCC13368. This recombinant system, with the co-expressed heterologous redox chain of the P450, bovine adrenodoxin reductase (AdR), and bovine adrenodoxin (Adx), was applied for the whole-cell conversion of KBA. The formation of 15α-hydroxy-KBA was increased 15-fold in comparison with the naturally CYP106A2-expressing B. megaterium strain ATCC 13368.

In a one‐step conversion, commercially available or known compounds are connected to form myrtucommulone A, an anti‐inflammatory and apoptosis‐inducing substance from the common myrtle Myrtus communis (see scheme). This strategy can be used, as well to prepare myrtucommulone libraries.

No abstract

In nur einer Stufe wird Myrtucommulon A, ein entzündungshemmender und Apoptose induzierender Inhaltsstoff der gemeinen Myrte Myrtus communis, aus käuflichen oder literaturbekannten Verbindungen synthetisiert (siehe Schema). Die Synthesestrategie ermöglicht ebenfalls die Erzeugung von Myrtucommulon‐Bibliotheken.