Microbial biotransformation of bioactive and clinically useful steroids and some salient features of steroids and biotransformation

Sultana, Nighat

doi:10.1016/j.steroids.2018.01.007

Cited by 58 publications

(27 citation statements)

References 100 publications

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“…Microbial biotransformation of drugs and/or their precursors to new molecules with modulated pharmacological profile is considered an invaluable tool in drug design and development [153]. The natural product class e steroids, are key substrates in this regard [154]. Accordingly, naturally occurring androstane steroid hormone, 5-dehydroepiandrosterone (47, Fig.…”

Section: Terpenoids and Steroidsmentioning

confidence: 99%

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

107

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BiomarkerEnzyme inhibition Molecular target Structure activity relationship a b s t r a c tThe emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, b-glucuronidase (bGLU) e a lysosomal acid hydrolase responsible for the catalytic deconjugation of b-D-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of bGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of bGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved bGLU inhibitory potency and the development of new therapeutic agents in consequential.

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Section: Terpenoids and Steroidsmentioning

confidence: 99%

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

107

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“…This effective strategy could facilitate pharmacologist to identify and quantify of MT extracts in the medicine market ( 67 ). In addition, given biotransformation in vivo may influence the chemical structure of a compound and change its activity ( 68 ), identification of metabolic characteristics could provide valuable information for further understanding the anti-tumor activity of MT. Using the ultra-HPLC coupled with high-resolution MS assay, Zhao et al identified the metabolic profile of C-21 steroids from MT for the first time.…”

Section: Safety and Efficacymentioning

confidence: 99%

The Antitumor Activities of Marsdenia tenacissima

et al. 2018

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Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.

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“…Steroids, including phytosterols and cholesterol, are ubiquitous in nature and significant growth substrates for microorganisms. Steroids are biologically active organic compounds that function either as important components of cell membranes or as signaling molecules [1]. Typically, steroid medicinal compounds share a tetracyclic hydrocarbon ring or gonane structure with different functional groups attached to C17-site.…”

Section: Introductionmentioning

confidence: 99%

Whole-genome and enzymatic analyses of an androstenedione-producing Mycobacterium strain with residual phytosterol-degrading pathways

et al. 2020

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Mycobacterium neoaurum strains can transform phytosterols to 4-androstene-3,17-dione (4-AD), a key intermediate for the synthesis of advanced steroidal medicines. In this work, we presented the complete genome sequence of the M. neoaurum strain HGMS2, which transforms β-sitosterol to 4-AD. Through genome annotation, a phytosterol-degrading pathway in HGMS2 was predicted and further shown to form a 9,10-secosteroid intermediate by five groups of enzymes. These five groups of enzymes included three cholesterol oxidases (ChoM; group 1: ChoM1, ChoM2 and Hsd), two monooxygenases (Mon; group 2: Mon164 and Mon197), a set of enzymes for side-chain degradation (group 3), one 3-ketosteroid-1,2-dehydrogenase (KstD; group 4: KstD211) and three 3-ketosteroid-9a-hydroxylases (Ksh; group 5: KshA226, KshA395 and KshB122). A gene cluster encoding Mon164, KstD211, KshA226, KshB122 and fatty acid β-oxidoreductases constituted one integrated metabolic pathway, while genes encoding other key enzymes were sporadically distributed. All key enzymes except those from group 3 were prepared as recombinant proteins and their activities were evaluated, and the proteins exhibited distinct activities compared with enzymes identified from other bacterial species. Importantly, we found that the KstD211 and KshA395 enzymes in the HGMS2 strain retained weak activities and caused the occurrence of two major impurities, i.e., 1,4-androstene-3,17-dione (ADD) and 9-hydroxyl-4-androstene-3,17-dione (9OH-AD) during β-sitosterol fermentation. The concurrence of these two 4-AD analogs not only lowered 4-AD production yield but also hampered 4-AD purification. HGMS2 has the least number of genes encoding KstD and Ksh enzymes compared with current industrial strains. Therefore, HGMS2 could be a potent strain by which the 4-AD production yield could be enhanced by disabling the KstD211 and KshA395 enzymes. Our work also provides new insight into the engineering of the HGMS2 strain to produce ADD and 9OH-AD for industrial application.

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Microbial biotransformation of bioactive and clinically useful steroids and some salient features of steroids and biotransformation

Cited by 58 publications

References 100 publications

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

The Antitumor Activities of Marsdenia tenacissima

Whole-genome and enzymatic analyses of an androstenedione-producing Mycobacterium strain with residual phytosterol-degrading pathways

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