Enhancement of Herboxidiene Production in Streptomyces chromofuscus ATCC 49982

2014 ◽  
Vol 24 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Amit Kumar Jha ◽  
Janardan Lamichhane ◽  
Jae Kyung Sohng
1999 ◽  
Vol 25 (5) ◽  
pp. 229-237
Author(s):  
Toshihiro WATANABE ◽  
Hiroaki SATO ◽  
Yozo NAKAZAWA ◽  
Yoshimasa SAGANE ◽  
T. Tsuneo KOZIMA ◽  
...  

2020 ◽  
Vol 295 (21) ◽  
pp. 7289-7300 ◽  
Author(s):  
Geetika Aggarwal ◽  
Jonah E. Zarrow ◽  
Zahra Mashhadi ◽  
C. Robb Flynn ◽  
Paige Vinson ◽  
...  

N-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and N-acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC50 of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC50 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC50 of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC50 = ∼2 μm) being symmetrically substituted dichlorophenes, i.e. hexachlorophene and bithionol. Structure–activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as Streptomyces chromofuscus PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD versus other tissue-associated lipases.


1992 ◽  
Vol 38 (10) ◽  
pp. 1022-1025 ◽  
Author(s):  
Marina Basaglia ◽  
Giuseppe Concheri ◽  
Stefano Cardinali ◽  
Maria B. Pasti-Grigsby ◽  
Marco P. Nuti

Eleven actinomycetes, isolated from the gut of worker termites (Macrotermes, Armitermes, Microcerotermes, Odontotermes), were identified as Streptomyces chromofuscus, S. chromogenus, S. diastaticus, and S. rochei. Their ability to grow on natural lignocellulosic substrates was tested in solid state fermentation experiments using wheat straw (C/N = 49.8) as a sole carbon source. Weight loss was 4.7–20.9% of the initial substrate, after 5 weeks at 30 °C; lignin and cellulose content decreased 2.0–16.1 and 3.5–32.9%, respectively. When the 11 Streptomyces were grown on wheat straw pretreated with (NH4)HCO3 (C/N = 28.2), weight loss was 9.3–29.9% of the initial substrate, indicating an overall enhancement of lignocellulose degradation. Weight, lignin, and cellulose losses were enhanced when S. chromofuscus (strain A2 and A11) and S. rochei A4 were grown on pretreated wheat straw instead of the untreated substrate. With S. rochei A10 the weight loss and lignin degradation were enhanced, while cellulolysis was slightly depressed. Weight loss and cellulose degradation were both enhanced when the remaining strains were grown on pretreated wheat straw. In this case, lignin degradation was depressed (S. chromofuscus A6 and A8, S. diastaticus A12, S. rochei A14) or remained essentially the same (S. diastaticus A3 and S. chromogenus A7). Key words: Streptomyces, wheat straw, degradation, lignin, cellulose.


1992 ◽  
Vol 45 (6) ◽  
pp. 914-921 ◽  
Author(s):  
MARGARET MILLER-WIDEMAN ◽  
NARINDER MAKKAR ◽  
MINHTIEN TRAN ◽  
BARBARA ISAAC ◽  
NANCY BIEST ◽  
...  

2003 ◽  
Vol 270 (22) ◽  
pp. 4523-4530 ◽  
Author(s):  
Karim El Kirat ◽  
Annie-France Prigent ◽  
Jean-Paul Chauvet ◽  
Bernard Roux ◽  
Francoise Besson

2012 ◽  
Vol 78 (6) ◽  
pp. 2034-2038 ◽  
Author(s):  
Lei Shao ◽  
Jiachen Zi ◽  
Jia Zeng ◽  
Jixun Zhan

ABSTRACTThe 53-kb biosynthetic gene cluster for the novel anticholesterol natural product herboxidiene was identified inStreptomyces chromofuscusATCC 49982 by genome sequencing and gene inactivation. In addition to herboxidiene, a biosynthetic intermediate, 18-deoxy-herboxidiene, was also isolated from the fermentation broth ofS. chromofuscusATCC 49982 as a minor metabolite.


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