Production of Androgens by Microbial Transformation of Progesterone in Vitro: A Model for Androgen Production in Rivers Receiving Paper Mill Effluent

We have previously documented the presence of progesterone and androstenedione in the water column and bottom sediments of the Fenholloway River, Taylor County, Florida. This river receives paper mill effluent and contains masculinized female mosquitofish. We hypothesized that plant sterols (e.g., β-sitosterol) derived from the pulping of pine trees are transformed by bacteria into progesterone and subsequently into 17α-hydroxyprogesterone, androstenedione, and other androgens. In this study, we demonstrate that these same androgens can be produced in vitro from the bacterium Mycobacterium smegmatis. In a second part to this study, we reextracted and reanalyzed the sediment from the Fenholloway River and verified the presence of androstadienedione, a Δ1 steroid with androgen activity

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons

13 p.-3 fig.-3 tab.A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage of natural sterols as an alternative to multistep chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc2155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains. Nevertheless, this property has not been exploited for the industrial production of steroidic synthons. Taking advantage of our knowledge on the cholesterol degradation pathway of M. smegmatis mc2155 we have demonstrated that the MSMEG_6039 (kshB1) and MSMEG_5941 (kstD1) genes encoding a reductase component of the 3-ketosteroid 9a-hydroxylase (KshAB) and a ketosteroid D1-dehydrogenase (KstD), respectively, are indispensable enzymes for the central metabolism of cholesterol. Therefore, wehave constructed a MSMEG_6039 (kshB1) gene deletion mutant of M. smegmatis MS6039 that transforms efficiently natural sterols (e.g. cholesterol and phytosterols) into 1,4-androstadiene-3,17-dione. In addition,we have demonstrated that a double deletion mutant M. smegmatis MS6039-5941 [DMSMEG_6039 (DkshB1)and DMSMEG_5941 (DkstD1)] transforms natural sterols into 4-androstene-3,17-dione with high yields.These findings suggest that the catabolism of cholesterol in M. smegmatis mc2155 is easy to handle and equally efficient for sterol transformation than other industrial strains, paving the way for valuating this strain as a suitable industrial cell factory to develop à la carte metabolic engineering strategies for the industrial production of pharmaceutical steroids.This study was supported by grants from the Ministry of Science and Innovation (BFU2006-15214-C03-01, BFU2009-11545-C03-03) and Ministry of Economy and Competitiveness (BIO2012-39695-C02-01).Peer reviewe

The Potential for Acupuncture to Mediate Hippocampal Apoptosis: A Systematic Review

Apoptosis is programmed cell death that can be maladaptive when not properly regulated, especially when it occurs in the hippocampus. The exact mechanisms for apoptotic malfunctioning are yet to be fully understood. Acupuncture has seen a recent rise in western medicine and is used to treat various blood flow related conditions such as strokes or ischemia. The exact mechanisms for acupuncture are also still unknown. This systematic review evaluated the potential for acupuncture to help mediate hippocampal apoptosis. A search was conducted through PubMed, Scopus, and WebofScience using the keywords “hippocampus,” “apoptosis,” and “acupuncture” and found 37 qualified articles from January 2009 to March 2019. All of the articles supported acupuncture decreasing the incidence of hippocampal apoptosis. The most frequently suggested mechanism was decreased BAX expression and increased BCL-2 expression, often in the CA1 region of the hippocampus; although, it was only seen in about 1/3 of the articles. While no exact mechanism is understood within current literature, acupuncture does indeed have the potential to mediate hippocampal apoptosis