The Mechanism of the Microbial Hydroxylation of Steroids. Part 2. Hydroxylation of a Δ4-3-Ketosteroid Analog by Rhizopus arrhizus ATCC 11145

1975 ◽  
Vol 53 (14) ◽  
pp. 2041-2044 ◽  
Author(s):  
Herbert L. Holland ◽  
Barbara J. Auret
Keyword(s):  
Transition State ◽  
Rhizopus Arrhizus ◽  
Microbial Hydroxylation ◽  
Microbial C

The Δ4-3-ketosteroid analog (± )-4a-methyl-4,4a,5,6,7,8-hexahydro-2(3H) naphthalenone (1) is hydroxylated at both C-8α and C-8β by Rhizopusarrhizus ATCC 11145. The ratio of C-8α to C-8β hydroxylation is compared with that obtained from the peracid oxidation of 2-ethoxy-4a-methyl-3,4,4a,5,6,7-hexahydronaphthalene (4) and a mechanism is proposed for both microbial and chemical hydroxylation in which the stereochemistry of the product is transition state controlled. The significance of this to the mechanism of microbial C-6β hydroxylation of Δ4-3-ketosteroids is discussed.

The Mechanism of The Microbial Hydroxylation of Steroids. Part 1. The C-21 Hydroxylation of Progesterone by Aspergillusniger ATCC 9142

1975 ◽  
Vol 53 (6) ◽  
pp. 845-854 ◽  
Author(s):  
Herbert L. Holland ◽  
Barbara J. Auret
Keyword(s):  
Hydrogen Bond ◽  
Carbonyl Group ◽  
Isotope Effect ◽  
Enol Form ◽  
Deuterium Isotope Effect ◽  
Rate Determining Step ◽  
Microbial Hydroxylation ◽  
Hydroxylation Reaction ◽  
Microbial C

The mechanism of the C-21 hydroxylation of progesterone (1a) by Aspergillusniger ATCC 9142 to give 11-deoxycorticosterone (1b) has been studied by the use of progesterone derivatives and of C-21 deuterium labelled progesterones. The requirement of the C-21 hydroxylase system for a C-20 carbonyl group is demonstrated and the possibility of the involvement of this group, in the C-20,21 enol form, in the C-21 hydroxylation reaction has been discussed. However, on the basis of the observed deuterium isotope effect (KH/KD = 1.25), a mechanism for the microbial C-21 hydroxylation reaction is proposed in which the rate-determining step is the direct insertion of oxygen into a C-21 carbon–hydrogen bond and not one involving enolization of the C-20 carbonyl.In addition, C-11α and C-15β hydroxylation of both 20α- and 20β-hydroxypregn-4-ene-3-one (2a and 2b) by A. niger has been observed.

Microbial hydroxylation of steroids. 5. Metabolism of androst-5-ene-3,17-dione and related compounds by Rhizopusarrhizus ATCC 11145

1979 ◽  
Vol 57 (4) ◽  
pp. 436-440 ◽  
Author(s):  
Herbert L. Holland ◽  
Peter R. P. Diakow
Keyword(s):  
Rhizopus Arrhizus ◽  
Microbial Hydroxylation ◽  
Related Compounds

The products of the incubation of androst-5-ene-3,17-dione (2a), 3β-hydroxyandrost-5-ene-17-one (2b), and androsta-3,5-diene-17-one (3) with Rhizopus arrhizus ATCC 11145 under a variety of conditions have been identified and the mechanisms of their formation discussed. In addition, several C-(4,5)- and C-(5,6)-epoxyandrostanes have been incubated with R. arrhizus, the products identified and possible pathways for their formation presented.

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

Collisional dynamics of Ca1D + HBr reactions: evidence for transition-state motions

1999 ◽  
Vol 97 (8) ◽  
pp. 967-976 ◽  
Author(s):  
M. Garay Salazar, J. M. Orea Rocha, A.
Keyword(s):  
Transition State ◽  
Collisional Dynamics

Pyogranulomatous obliterative laryngotracheitis by Rhizopus arrhizus (syn. R. oryzae) in a free-ranging Atlantic spotted dolphin Stenella frontalis

2018 ◽  
Vol 130 (2) ◽  
pp. 153-158
Author(s):  
A Cerezo ◽  
O Quesada-Canales ◽  
E Sierra ◽  
J Díaz-Delgado ◽  
A Fernández ◽  
...  
Keyword(s):  
Rhizopus Arrhizus ◽  
Stenella Frontalis ◽  
Spotted Dolphin ◽  
Free Ranging
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