High-Titer Production of Olivetolic Acid and Analogs in Engineered Fungal Host Using a Nonplant Biosynthetic Pathway

2021 ◽  
Author(s):  
Ikechukwu C. Okorafor ◽  
Mengbin Chen ◽  
Yi Tang
Keyword(s):  
Biosynthetic Pathway ◽  
High Titer ◽  
Fungal Host

scholarly journals The Final Step of Hygromycin A Biosynthesis, Oxidation of C-5″-Dihydrohygromycin A, Is Linked to a Putative Proton Gradient-Dependent Efflux

2009 ◽  
Vol 53 (12) ◽  
pp. 5163-5172 ◽  
Author(s):  
Vidya Dhote ◽  
Agata L. Starosta ◽  
Daniel N. Wilson ◽  
Kevin A. Reynolds
Keyword(s):  
Biosynthetic Pathway ◽  
High Titer ◽  
Biosynthetic Gene Cluster ◽  
Proton Gradient ◽  
Purification And Characterization ◽  
E Coli ◽  
Reduced Activity

ABSTRACT Hygromycin A (HA) is an aminocyclitol antibiotic produced and excreted by Streptomyces hygroscopicus. Deletion of hyg26 from the hygromycin A biosynthetic gene cluster has previously been shown to result in a mutant that produces 5″-dihydrohygromycin A (DHHA). We report herein on the purification and characterization of Hyg26 expressed in E scherichia coli. The enzyme catalyzes an NAD(H)-dependent reversible interconversion of HA and DHHA, supporting the role of the reduced HA as the penultimate biosynthetic pathway intermediate and not a shunt product. The equilibrium for the Hyg26-catalyzed reaction heavily favors the DHHA intermediate. The high-titer production of the HA product by S. hygroscopicus must be dependent upon a subsequent energetically favorable enzyme-catalyzed process, such as the selective and efficient export of HA. hyg19 encodes a putative proton gradient-dependent transporter, and a mutant lacking this gene was observed to produce less HA and to produce the DHHA intermediate. The DHHA produced by either the Δhyg19 or the Δhyg26 mutant had slightly reduced activity against E. coli and reduced protein synthesis-inhibitory activity in vitro. The data indicate that Hyg26 and Hyg19 have evolved to produce and export the final potent HA product in a coordinated fashion.

scholarly journals Fusarium oxysporum f. sp. dianthi virus 1 Accumulation Is Correlated with Changes in Virulence and Other Phenotypic Traits of Its Fungal Host

2018 ◽  
Vol 108 (8) ◽  
pp. 957-963 ◽  
Author(s):  
Carlos Germán Lemus-Minor ◽  
M. Carmen Cañizares ◽  
María Dolores García-Pedrajas ◽  
Encarnación Pérez-Artés
Keyword(s):  
Fusarium Oxysporum ◽  
High Titer ◽  
Phenotypic Traits ◽  
High Accumulation ◽  
Double Stranded Rna ◽  
Fungal Host ◽  
Potential Biocontrol Agent ◽  
Residual Level ◽  
Total Dna ◽  
Rna Accumulation

Fusarium oxysporum f. sp. dianthi virus 1 (FodV1) was detected in isolate 116 (116V+) of Fusarium oxysporum f. sp. dianthi, reaching such a high accumulation level that it was clearly visible after agarose gel electrophoresis of total DNA extracts. FodV1 consists of four double-stranded RNA segments that correspond to a new mycovirus in the Chrysoviridae family. We obtained an isolate of F. oxysporum f. sp. dianthi 116 (116V−) with only a residual level of FodV1 RNA accumulation by single-conidia selection. Compared with 116V−, isolate 116V+ showed significant phenotypic alterations in vegetative growth and virulence. Thus, the presence of a high titer of mycovirus FodV1 was associated with a modified morphology and a reduced growth of the colonies on solid medium, and with a diminished conidiation in liquid medium. Inoculation of four susceptible carnation cultivars with either 116V− or 116V+ showed that the presence of a high titer of FodV1 was also correlated with a significantly reduced virulence of its fungal host. All of the results suggest that FodV1 could be associated with hypovirulence, identifying it as a potential biocontrol agent for Fusarium wilt of carnation. This is the first report of a mycovirus potentially associated with the induction of hypovirulence in the species F. oxysporum.

New insights into heparan sulphate biosynthesis from the study of mutant mice

2002 ◽  
Vol 69 ◽  
pp. 47-57 ◽  
Author(s):  
Catherine L. R. Merry ◽  
John T. Gallagher
Keyword(s):  
Growth Factors ◽  
Biosynthetic Pathway ◽  
Heparan Sulphate ◽  
Mutant Mice ◽  
Gene Products ◽  
Multiple Gene ◽  
Adhesion Proteins ◽  
Ligand Interactions

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.

Inhibitorentwicklung nach früher hoher Exposition und Hirnblutung

2010 ◽  
Vol 30 (S 01) ◽  
pp. S115-S118
Author(s):  
C. Moorthi ◽  
A. Bade ◽  
C. Niekrens ◽  
G. Auerswald ◽  
K. Haubold
Keyword(s):  
High Titer ◽  
Cerebral Haemorrhage ◽  
High Dose ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Intron 22 Inversion ◽  
Neurosurgical Intervention

SummarySevere haemophilia A was diagnosed postpartum in a newborn. The mother was known as a conductor (intron 22 inversion) and an uncle had a persistently high titer inhibitor after failed ITI.Due to a cephalhaematoma, a high-dose pdFVIII substitution was given within the first days after birth. At the age of six month a severe cerebral haemorrhage occurred, making a high-dose pdFVIII substitution and neurosurgical intervention necessary. Several days later a porth-a-cath-system was implanted. The development of a high titer inhibitor occured six days later, an ITI was started according to the Bonn Protocol. Initially rFVIIa was given in addition to the pdFVIII substitution. Seven days after the beginning of treatment the inhibitor was no longer detectable. At monthly intervals the FVIII dosage was reduced until the dosage complied with a prophylaxis in severe haemophilia A.The duration of the ITI was nine months. A total of 30 mg rFVIIa and 276 000 IU pdFVIII were used; costs in total: 280 173.60 Euro.

A Case of Dermatomyositis with High-titer Anti-toxoplasma Antibody

2006 ◽  
Vol 68 (2) ◽  
pp. 138-141
Author(s):  
Yukie WATANABE ◽  
Akimichi MORITA
Keyword(s):  
High Titer
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