Faculty Opinions recommendation of Engineering cellular metabolite transport for biosynthesis of computationally predicted tropane alkaloid derivatives in yeast.

Author(s):  
Kazuki Saito ◽  
Tsubasa Shoji
2021 ◽  
Vol 118 (25) ◽  
pp. e2104460118
Author(s):  
Prashanth Srinivasan ◽  
Christina D. Smolke

Microbial biosynthesis of plant natural products (PNPs) can facilitate access to valuable medicinal compounds and derivatives. Such efforts are challenged by metabolite transport limitations, which arise when complex plant pathways distributed across organelles and tissues are reconstructed in unicellular hosts without concomitant transport machinery. We recently reported an engineered yeast platform for production of the tropane alkaloid (TA) drugs hyoscyamine and scopolamine, in which product accumulation is limited by vacuolar transport. Here, we demonstrate that alleviation of transport limitations at multiple steps in an engineered pathway enables increased production of TAs and screening of useful derivatives. We first show that supervised classifier models trained on a tissue-delineated transcriptome from the TA-producing plant Atropa belladonna can predict TA transporters with greater efficacy than conventional regression- and clustering-based approaches. We demonstrate that two of the identified transporters, AbPUP1 and AbLP1, increase TA production in engineered yeast by facilitating vacuolar export and cellular reuptake of littorine and hyoscyamine. We incorporate four different plant transporters, cofactor regeneration mechanisms, and optimized growth conditions into our yeast platform to achieve improvements in de novo hyoscyamine and scopolamine production of over 100-fold (480 μg/L) and 7-fold (172 μg/L). Finally, we leverage computational tools for biosynthetic pathway prediction to produce two different classes of TA derivatives, nortropane alkaloids and tropane N-oxides, from simple precursors. Our work highlights the importance of cellular transport optimization in recapitulating complex PNP biosyntheses in microbial hosts and illustrates the utility of computational methods for gene discovery and expansion of heterologous biosynthetic diversity.


1991 ◽  
Vol 266 (7) ◽  
pp. 4648-4653
Author(s):  
T Hashimoto ◽  
A Hayashi ◽  
Y Amano ◽  
J Kohno ◽  
H Iwanari ◽  
...  

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 419
Author(s):  
Jordi Sardans ◽  
Josep Peñuelas

Potassium, mostly as a cation (K+), together with calcium (Ca2+) are the most abundant inorganic chemicals in plant cellular media, but they are rarely discussed. K+ is not a component of molecular or macromolecular plant structures, thus it is more difficult to link it to concrete metabolic pathways than nitrogen or phosphorus. Over the last two decades, many studies have reported on the role of K+ in several physiological functions, including controlling cellular growth and wood formation, xylem–phloem water content and movement, nutrient and metabolite transport, and stress responses. In this paper, we present an overview of contemporary findings associating K+ with various plant functions, emphasizing plant-mediated responses to environmental abiotic and biotic shifts and stresses by controlling transmembrane potentials and water, nutrient, and metabolite transport. These essential roles of K+ account for its high concentrations in the most active plant organs, such as leaves, and are consistent with the increasing number of ecological and agricultural studies that report K+ as a key element in the function and structure of terrestrial ecosystems, crop production, and global food security. We synthesized these roles from an integrated perspective, considering the metabolic and physiological functions of individual plants and their complex roles in terrestrial ecosystem functions and food security within the current context of ongoing global change. Thus, we provide a bridge between studies of K+ at the plant and ecological levels to ultimately claim that K+ should be considered at least at a level similar to N and P in terrestrial ecological studies.


2021 ◽  
Author(s):  
Jian-Ping Huang ◽  
Yong-Jiang Wang ◽  
Tian Tian ◽  
Li Wang ◽  
Yijun Yan ◽  
...  

From the first ambitious imagination of tropinone biosynthesis mechanism in plants published in 1917 to the de novo production of scopolamine in yeast realized in 2020, what did we learn from this long story of more than 100 years old?


2001 ◽  
Vol 29 (1) ◽  
pp. A2-A2
Author(s):  
R. J. A. Wanders ◽  
S. Ferdinandusse ◽  
G. A. Jansen ◽  
E. G. van Grusven ◽  
H. R. Waterham ◽  
...  

Xenobiotica ◽  
1991 ◽  
Vol 21 (10) ◽  
pp. 1289-1300 ◽  
Author(s):  
S. Wada ◽  
T. Yoshimitsu ◽  
N. Koga ◽  
H. Yamada ◽  
K. Oguri ◽  
...  

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