Cytochrome P450 102A1 (CYP102A1) (CYP102A1)

Cytochrome P450 BM3 (CYP102A1) from Bacillus megaterium is a soluble, self-sufficient monooxygenase that serves as a premier model for the cytochrome P450 superfamily [1, 2]. The heme domain of this enzyme contains the catalytic center where long-chain fatty acids are hydroxylated at sub-terminal positions with high efficiency [2]. Unlike human P450s, BM3 is naturally fused to its reductase partner, allowing for the highest known catalytic rates among P450 enzymes [2, 4]. While not a therapeutic target for human disease, it is a critical tool in biotechnology for the production of drug metabolites and the development of novel biocatalysts through directed evolution [3, 4]. Its heme domain is frequently used in structural biology to model drug-protein interactions and to study the fundamental mechanisms of oxygen activation [2, 3]. The enzyme's versatility has led to engineered variants capable of metabolizing a wide range of non-natural substrates, including human drugs like diclofenac and ibuprofen [3]. It is also used as a biosensor component due to its robust nature and well-understood electron transfer mechanisms [4]. In the pharmaceutical industry, it serves as a surrogate for human P450s in early-stage drug metabolism and pharmacokinetic (DMPK) studies [3]. Citations: [1] UniProt (P14779); [2] Munro et al. (2007) PMID: 17579474; [3] Whitehouse et al. (2012) doi:10.1039/C2CS35154D; [4] Girvan & Munro (2016) PMID: 27255410.

Other names

P450 BM3Cytochrome P450 BM3BMPFatty acid monooxygenaseCYP102A1

Substrate hydroxylation via a heme-thiolate catalytic cycle involving a high-valent iron-oxo intermediate (Compound I) [2].