scholarly journals Molecular Basis for Extender Unit Specificity of Mycobacterial Polyketide Synthases

2020 ◽  
Vol 15 (12) ◽  
pp. 3206-3216
Author(s):  
Anna D. Grabowska ◽  
Yoann Brison ◽  
Laurent Maveyraud ◽  
Sabine Gavalda ◽  
Alexandre Faille ◽  
...  
2005 ◽  
Vol 12 (10) ◽  
pp. 1145-1153 ◽  
Author(s):  
Alexandros P. Siskos ◽  
Abel Baerga-Ortiz ◽  
Shilpa Bali ◽  
Viktor Stein ◽  
Hassan Mamdani ◽  
...  

2018 ◽  
Author(s):  
Maja Klaus ◽  
Alicia D. D’Souza ◽  
Aleksandra Nivina ◽  
Chaitan Khosla ◽  
Martin Grininger

AbstractEngineering of assembly line polyketide synthases (PKSs) to produce novel bioactive compounds has been a goal for over twenty years. The apparent modularity of PKSs has inspired many engineering attempts in which entire modules or single domains were exchanged. In recent years, it has become evident that certain domain-domain interactions are evolutionarily optimized, and if disrupted, cause a decrease of the overall turnover rate of the chimeric PKS. In this study, we compared different types of chimeric PKSs in order to define the least invasive interface and to expand the toolbox for PKS engineering. We generated bimodular chimeric PKSs in which entire modules were exchanged, while either retaining a covalent linker between heterologous modules or introducing a non-covalent docking domain- or SYNZIP domain-mediated interface. These chimeric systems exhibited non-native domain-domain interactions during intermodular polyketide chain translocation. They were compared to otherwise equivalent bimodular PKSs in which a non-covalent interface was introduced between the condensing and processing parts of a module, resulting in non-native domain interactions during the extender unit acylation and polyketide chain elongation steps of their catalytic cycles. We show that the natural PKS docking domains can be efficiently substituted with SYNZIP domains and that the newly introduced non-covalent interface between the condensing and processing parts of a module can be harnessed for PKS engineering. Additionally, we established SYNZIP domains as a new tool for engineering PKSs by efficiently bridging non-native interfaces without perturbing PKS activity.


2021 ◽  
Author(s):  
Munro Passmore ◽  
Angelo Gallo ◽  
Józef Romuald Lewandowski ◽  
Matthew Jenner

The biosynthesis of polyketides by type I modular polyketide synthases (PKS) relies on co-ordinated interactions between acyl carrier protein (ACP) domains and catalytic domains within the megasynthase. Despite the importance...


Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.


Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.


1998 ◽  
Vol 33 ◽  
pp. 65-77 ◽  
Author(s):  
Dominique Massotte ◽  
Brigitte L. Kieffer
Keyword(s):  

2011 ◽  
Vol 81 (4) ◽  
pp. 238-239 ◽  
Author(s):  
Manfred Eggersdorfer ◽  
Paul Walter

Nutrition is important for human health in all stages of life - from conception to old age. Today we know much more about the molecular basis of nutrition. Most importantly, we have learnt that micronutrients, among other factors, interact with genes, and new science is increasingly providing more tools to clarify this interrelation between health and nutrition. Sufficient intake of vitamins is essential to achieve maximum health benefit. It is well established that in developing countries, millions of people still suffer from micronutrient deficiencies. However, it is far less recognized that we face micronutrient insufficiencies also in developed countries.


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