(節(jié)選）藥學(xué)專業(yè)畢業(yè)論文外文翻譯--黃酮類化合物的微生物和酶轉(zhuǎn)化(英文）

1、See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/7216130Microbial and Enzimatic Transformations ofFlavonoidsARTICLE in JOURNAL OF NATURAL PRODUCTS · APR

2、IL 2006Impact Factor: 3.8 · DOI: 10.1021/np0504659 · Source: PubMedCITATIONS64READS1622 AUTHORS, INCLUDING:John P N RosazzaUniversity of Iowa204 PUBLICATIONS 3,755 CITATIONS SEE PROFILEAvailable from: John

3、P N RosazzaRetrieved on: 29 January 2016lyase (BAL, EC 4.1.2.38).46 BAL, a thiamine pyrophosphate (TPP)- dependent enzyme from Pseudomonas fluorescens Biovar I, catalyzes cleavage of the alpha-ketol carbon-carbon bond of

4、 benzoin to form two benzaldehydes.46 BAL also catalyzes the reverse acyloin condensation of certain benzaldehydes, resulting in the synthesis of [R]-benzoins.47 Recombinant BAL was used to catalyze mixed acyloin condens

5、ations of a series of methoxyben- zaldehydes (9) and phenylacetaldehyde (10) to enantiomerically pure 2-hydroxy-1,3-diphenylpropan-1-ones (11), o-anisoins (12), and 1-hydroxy-1,3-diphenylpropan-2-ones (13) (Figure 2).48

6、R absolute configurations of chiral centers were established by CD spectroscopy. [R]-Hydroxydihydrochalcones and 1-hydroxy-1,3- diphenylpropan-2-ones are valuable synthons for chemoenzymatic syntheses of flavonoids. The

7、relaxed specificity of BAL enabled the synthesis of a variety of acyloin products. In general, tri- methoxybenzaldehydes were poor substrates, while dimethoxy benzaldehydes and especially those substituted in the meta po

8、sition gave fewer products in better yields.Few microbial transformation studies have been reported directly on chalcones. The unsubstituted chalcone 2 was converted to 2′′- hydroxychalcone (14) and 2′′,3′′-dihydroxychal

9、cone (15) (Figure 3) in 25% and 59% yields, respectively, by Escherichia coli carrying modified biphenyl dioxygenase [bphA1(2072)A2A3A4] and dihy- drodiol dehydrogenase genes (bphB).49Hydroxylated chalcone metabolites al

10、so have been reported when flavanone undergoes ring opening. Udupa et al.50 obtained 2′- hydroxy- and 2′,4′′-dihydroxychalcones and dihydrochalcones when (()-flavanone (5) was transformed by Gibberella fujikuroi. In this

11、early work, flavanone carbonyls were stereospecifically reduced to alcohols by this fungus. Similarly, Abul-Hajj et al. also reported 2′-hydroxydihydrochalcone, 2′,4′′-dihydroxydihydrochalcone, 2′,3′′,4′′- trihydroxydihy

12、drochalcone, and 2′,5′-dihydroxydihydrochalcone as metabolites of (()-flavanone by several microorganisms.51A series of microorganisms were screened for their abilities to mimic plant metabolism in cyclizing chalcones to

13、 flavonoids. Aspergillus alliaceus UI 315 cyclized 2′-hydroxy-2′′,3′′-dimethoxy- chalcone (16) to three flavanones, 17, 18, and 19, and to 3′′-O- demethylated (20) and 3′′-O-demethylated-3′-hydroxylated (21) chalcones (F

14、igure 4).52 Patterns of metabolites obtained from 16 with A. alliaceus cultures were dramatically altered when cyto- chrome P450 (CYP450) inhibitors SKF525A, metyrapone, and phenylthiocarbamide were included in culture m

15、edia. These inhibi- tors revealed that as many as three different CYP450 enzyme systems were involved in chalcone biotransformations. One enzyme catalyzed chalcone cyclization, forming 17, 18 and 19; a second CYP450 was

16、responsible for catalyzing 3′′-O-dealkylation of 16 and 17 to chalcone 20 and flavanone 18, respectively, while a third CYP450 catalyzed 3′-chalcone hydroxylation of 20 to 21. Flavanones obtained from A. alliaceus reacti

17、ons were racemic, whereas similar products formed in plants are not.52 In plants, chalcone isomerase catalyzes stereospecific chalcone cyclization to flavanones by an ionic 1,4-Michael addition with the R,?- unsaturated

18、carbonyl functionality. Sanchez and Rosazza speculated that the enzyme system of A. alliaceus catalyzed a nonstereospecific, radical-based, intramolecular cyclization of chalcones to flavanones. One earlier study on micr

19、obial transformations of xanthohumol (22) by Pichia membranifaciens gave flavanone (23) plus altered chalcones 24 and 25 in the only other example of a microbial chalcone cyclization (Figure 5).53Aurones were obtained wh

20、en differently substituted chalcones were biotransformed by A. alliaceus. 4′,2′′,4′′-Trihydroxychalcone (isoliquiritigenin, 26) was hydroxylated at position-3′ to form butein (27), which was cyclized to the aurone produc

21、t sulfuretin (30) (Figure 6) (unpublished results). Inhibition experiments showed that initial C-3′ hydroxylation of 26 to 27 was catalyzed by a CYP450 enzyme system. Partially purified A. alliaceus polyphenol oxidase, a

22、 catechol oxidase, cyclized 27 to 30. Thus, A. alliaceus uses a two-step process for aurone synthesis much like the plant biosyn- thetic pathway suggested by Nakayama et al.54 In the first step, cytochrome P450 hydroxyla

23、tes 26 at position 3′, giving 27, while the ring-forming step that produces the aurone is catalyzed by a catechol oxidase, likely via an o-quinone intermediate (28). Metabolic engineering in a common yeast, of components

24、 of the phenylpropanoid pathway, was used to prepare naringenin (33b), a central biosynthetic precursor of many flavonoids.55 Genes for phenylalanine ammonia lyase (PAL) from Rhodosporidium toru- loides, 4-coumarate:coen

25、zyme A (CoA) ligase (4CL) from Arabi- dopsis thaliana, and chalcone synthase (CHS) from Hypericum androsaemum were introduced into two Saccharomyces cereVisiaeFigure 2. BAL-catalyzed phenylacetaldehyde and benzaldehyde c

26、ondensation (R ) 2-MeO; 2,3-DiMeO; 2,4-DiMeO; 2,5-DiMeO; 3,5-DiMeO).Figure 3. Chalcone (2) and hydroxylated metabolites by recom- binant E. coli expressing biphenhyldioxygenase and dihydrodiol dehydrogenase.Figure 4. Bio