Candida parapsilosis

Chadha et al, have published a series of papers on the deracemization of P-hydroxyesters using whole cells of Candida parapsilosis. For example, deracemization of racemic ethyl 2-hydroxy-4-phenylbutanoic acid (22 R = H) yielded the (S) enantiomer in 85-90% yield and >99% ee (Figure 5.15) [26]. 

Figure 5.15 Deracemization of (3-hydroxyesters using Candida parapsilosis.

For reduction of acetylenic ketones, two oxidoreductases were used [25]. Lactobacillus brevis alcohol dehydrogenase (LBADH) gave the (R)-alcohols and Candida parapsilosis carbonyl reductase (CPCR) afforded the (S)-isomer, both in good yield and excellent enantioselectivity. By changing the steric demand of the substituents, the enantiomeric excess values can be adjusted and even the configurations of the products can be altered (Figure 8.34). 

The ability to grow at the expense of 4-hydroxy- and 3,4-dihydroxybenzoate has been nsed for the classification of medically important yeasts inclnding Candida parapsilosis (Cooper and Land 1979). This organism degrades these snbstrates by oxidative decarboxylation, catalyzed by a flavoprotein monooxygenase (Eppink et al. 1997). 

Cooper BH, GA Land (1979) Assimilation of protocatechnate acid and p-hydroxybenzoic acid as an aid to laboratory identification of Candida parapsilosis and other medically important yeasts. J Clin Microbiol 10 343-345. 

Hydroxybenzoates can nndergo hydroxylation with or withont concomitant loss of CO2. For example, salicylate —> catechol + CO2 (salicylate-l-hydroxylase) (Fignre 3.9a) (White-Stevens et al. 1972) and 4-hydroxybenzoate —> 1,4-dihydroxybenzene + CO2 [(4-hydroxy-benzoate 1-hydroxylase (decarboxylating)] in Candida parapsilosis (Fignre 3.9b) (Eppink etal. 1997). 

Eppink MHM, SA Boeren, J Vervoort, WJH van Berkel (1997) Purification and properties of 4-hydroxybenzoate 1-hydroxylase (decarboxylating), a novel flavin adenine dinucleotide-dependent monooxygenase from Candida parapsilosis CBS604. J Bacterial 179 668-6687. 

Oxidative decarboxylation of hydroxybenzoates by the yeast Candida parapsilosis is catalyzed by a flavin monooxygenase that is able to use a range of fluorinated hydroxybenzoates that were examined by F NMR (Eppink et al. 1997). 

O The predominant pathogen associated with vulvovaginal candidiasis is Candida albicans, although a small percentage of cases are caused by Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsilosis. 

Candida albicans accounts for 80% of cases of OPC and esophageal candidiasis. Over the last 20 years, an increasing incidence of C. albicans resistance has been accompanied by an increased incidence of non-albicans species infections, including Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsilosis. In patients with cancer, non-albicans Candida species account for almost half of all cases.29... 

Patel and coworkers reported that microbial reduction of ethyl l-benzyl-3-oxopiperidine-4-carboxylate by Candida parapsilosis SC16 347 gave ethyl cis-(3R,4R)-1 -benzyl-3AMiydro-xypiperidine-4/ -carboxylate as the major product in 97.4% diastereomeric excess (de) and 99.8% ee (Figure 7.2), while 99.5% de and 98.2% ee were achieved in the reduction catalyzed by Pichia methanolica SC16 415 [14]. 

Hasegawa and co-workers [18] screened a number of microorganisms for the ability to degrade or deracemize selectively terminal 1,2-diols, useful intermediates for the synthesis of pharmacueticals, agrochemicals and liquid crystals. The yeast Candida parapsilosis IFO 0708 was the strain of choice for deracemization of the model substrate, pentan-l,2-diol 19. This biotransfor-... 

Candida parapsilosis was found to be able to convert (k)-1,2-butanediol to (S)-l,2-butanediol through stereospecific oxidation and asymmetric reduction reactions [72]. The oxidation of (k)-1,2-butanediol to l-hydroxy-2-butanone and the reduction of l-hydroxy-2-butanone to (S)-l,2-butanediol were cataly-... 

Fig. 4. Activity of an alcohol dehydrogenase (carhonyl reductase from Candida parapsilosis 0.13 mg/ml) reducing 2-hutanone (0.67 mol/1) depending on the composition (y/wd of the microemulsion (Marlipal O13-60/Water/Cyclohexane) at pH 7. The cofactor concentration is Cnadh =115 pmol/1...

In a photometric assay NADP(H)-dependent LBADH (see above) [9] and NAD(H) -dependent Candida parapsilosis carbonyl reductase (CPCR) [40] were identified as suitable catalysts accepting a broad range of ynones as substrates. Both enzymes catalyze the reduction of various aryl alkynones 21 with high enantioselectivity and efficiency (Scheme 2.2.7.13) [41]. 

R. erythropolis Rhodococcus erythropolis CPCR Candida parapsilosis carbonyl reductase ... 

In a direct comparison of the reduction of acetophenone to highly enantio-en-riched (R)-phenylethanol (94% e.e.) by heterogenized (S)-diphenyloxazaborolidine (Corey-Itsuno catalyst) or to enantiomerically pure (S)-phenylethanol (> 99% e.e.) by Candida parapsilosis carbonyl reductase (CPCR), the superior solubility of acetophenone in THF (0.25 m) versus water (0.04 m) leads to a vastly superior space-time yield of 290 g (L d) 1 in THF with the Corey-Itsuno catalyst in comparison with 27 g (L d) 1 in water with CPCR (Rissom, 1999). Conversely, the turnover frequencies (tofs) of 0.3 min-1 (Corey-Itsuno catalyst) versus 2.3 x 104 min-1 (CPCR) portend the difference in total turnover number (TTNs) of 2.4 x 108 versus 560. 

The enzyme catalyzing the reduction of ketopantolactone to D-pantolactone was isolated in a crystalline form from the cells of Candida parapsilosis and characterized in some detail [106] (see Tables 4 and 5). It is a novel NADPH-dependent carbonyl reductase with a molecular mass of about 40,000. In addition to the reduction of ketopantolactone, the enzyme catalyzes those of a variety of cyclic diketones, including derivatives of ketopantolactone, isatin, camphorquinone and so on, to give the corresponding (R)-alcohols [106, 107], The enzyme was termed conjugated polyketone reductase , since the enzyme catalyzes only the reduction of conjugated polyketones as follows. 

The /3-D-glucopyranans of Candida albicans serotype B and Candida parapsilosis are mainly linear, with only 10% of branch points, and contain, principally, (l- 6) linkages (67 and 63%, respectively).59... 

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