Bacillus megaterium CYP102A1 Oxidation of Acyl Homoserine Lactones and Acyl Homoserines
详细信息 查看全文
- 作者：Puneet K. Chowdhary ; Neela Keshavan ; Hien Q. Nguyen ; Julian A. Peterson ; Juan E. Gonzá ; lez ; Donovan C. Haines
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：December 18, 2007
- 年：2007
- 卷：46
- 期：50
- 页码：14429 - 14437
- 全文大小：129K
- 年卷期：v.46,no.50(December 18, 2007)
- ISSN：1520-4995
文摘
Quorum sensing, the ability of bacteria to sense their own population density through thesynthesis and detection of small molecule signals, has received a great deal of attention in recent years.Acyl homoserine lactones (AHLs) are a major class of quorum sensing signaling molecules. In nature,some bacteria that do not synthesize AHLs themselves have developed the ability to degrade thesecompounds by cleaving the amide bond or the lactone ring. By inactivating this signal used by competingbacteria, the degrading microbe is believed to gain a competitive advantage. In this work we report thatCYP102A1, a widely studied cytochrome P450 from Bacillus megaterium, is capable of very efficientoxidation of AHLs and their lactonolysis products acyl homoserines. The previously known substratesfor this enzyme, fatty acids, can also be formed in nature by hydrolysis of the amide of AHLs, so CYP102A1is capable of inactivating the active parent compound and the products of both known pathways for AHLinactivation observed in nature. AHL oxidation primarily takes place at the -1, -2, and -3 carbons ofthe acyl chain, similar to this enzyme's well-known activity on fatty acids. Acyl homoserines and theirlactones are better substrates for CYP102A1 than fatty acids. Bioassay of the quorum sensing activity ofoxidation products reveals that the subterminally hydroxylated AHLs exhibit quorum sensing activity,but are 18-fold less active than the parent compound. In vivo, B. megaterium inactivates AHLs by aCYP102A1 dependent mechanism that must involve additional components that further sequester ormetabolize the products, eliminating their quorum sensing activity. Cytochrome P450 oxidation of AHLsrepresents an important new mechanism of quorum quenching.