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- Li, Qishuang, et al.
(författare)
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Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast
- 2024
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Ingår i: Journal of Integrative Plant Biology. - 1672-9072 .- 1744-7909. ; 66:8, s. 1703-1717
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Tidskriftsartikel (refereegranskat)abstract
- Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A- and D-rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)-glaziovine, (S)-glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.
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| 2. |
- Zhang, Cong, et al.
(författare)
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Association of Metabolic Syndrome with Macular Thickness and Volume in Older Adults : A Population-Based Optical Coherence Tomography Study
- 2024
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Ingår i: Metabolic Syndrome and Related Disorders. - 1540-4196 .- 1557-8518. ; 22:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults.Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018–2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models.Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted β = −5.29; 95% confidence interval: −9.31 to −1.26), parafoveal (−2.85; −5.73 to 0.04) and perifoveal regions (−4.37; −6.79 to −1.95) when using the IDF criteria, in the perifoveal regions (−3.82; −6.18 to −1.47) when using the IDF/AHA criteria, and in the central region (−5.63; −10.25 to −1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (−0.16; −0.26 to −0.07) and IDF/AHA (−0.13; −0.22 to −0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (β = −6.25; −10.94 to −1.56) but not in women. Abdominal obesity (−2.83; −5.41 to −0.25) and elevated fasting blood glucose (−2.65; −5.08 to −0.21) were associated with thinner macular thickness in the perifoveal region.Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS.
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