Faculty Opinions recommendation of Bioengineering natural product biosynthetic pathways for therapeutic applications.

Author(s):  
Jean-Jacques Sanglier
2012 ◽  
Vol 23 (6) ◽  
pp. 931-940 ◽  
Author(s):  
Ming-Cheng Wu ◽  
Brian Law ◽  
Barrie Wilkinson ◽  
Jason Micklefield

iScience ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 100795
Author(s):  
Hengqian Ren ◽  
Chengyou Shi ◽  
Huimin Zhao

2018 ◽  
Vol 35 (8) ◽  
pp. 707-720 ◽  
Author(s):  
Susan C. Wang

This highlight examines the functions of cobalamin-dependent radicalS-adenosyl-l-methionine enzymes that catalyse chemically-challenging reactions in several bacterial natural product biosynthetic pathways.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Bohdan Bilyk ◽  
Sora Kim ◽  
Asif Fazal ◽  
Tania A. Baker ◽  
Ryan F. Seipke

ABSTRACT The survival of any microbe relies on its ability to respond to environmental change. Use of extracytoplasmic function (ECF) RNA polymerase sigma (σ) factors is a major strategy enabling dynamic responses to extracellular signals. Streptomyces species harbor a large number of ECF σ factors, nearly all of which are uncharacterized, but those that have been characterized generally regulate genes required for morphological differentiation and/or response to environmental stress, except for σAntA, which regulates starter-unit biosynthesis in the production of antimycin, an anticancer compound. Unlike a canonical ECF σ factor, whose activity is regulated by a cognate anti-σ factor, σAntA is an orphan, raising intriguing questions about how its activity may be controlled. Here, we reconstituted in vitro ClpXP proteolysis of σAntA but not of a variant lacking a C-terminal di-alanine motif. Furthermore, we show that the abundance of σAntA in vivo was enhanced by removal of the ClpXP recognition sequence and that levels of the protein rose when cellular ClpXP protease activity was abolished. These data establish direct proteolysis as an alternative and, thus far, unique control strategy for an ECF RNA polymerase σ factor and expands the paradigmatic understanding of microbial signal transduction regulation. IMPORTANCE Natural products produced by Streptomyces species underpin many industrially and medically important compounds. However, the majority of the ∼30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. This unrevealed biochemical diversity is believed to comprise an untapped resource for natural product drug discovery. Major roadblocks preventing the exploitation of unexpressed biosynthetic pathways are a lack of insight into their regulation and limited technology for activating their expression. Our findings reveal that the abundance of σAntA, which is the cluster-situated regulator of antimycin biosynthesis, is controlled by the ClpXP protease. These data link proteolysis to the regulation of natural product biosynthesis for the first time to our knowledge, and we anticipate that this will emerge as a major strategy by which actinobacteria regulate production of their natural products. Further study of this process will advance understanding of how expression of secondary metabolism is controlled and will aid pursuit of activating unexpressed biosynthetic pathways.


2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.


2017 ◽  
Vol 5 (6) ◽  
Author(s):  
Shukria Akbar ◽  
Scot E. Dowd ◽  
D. Cole Stevens

ABSTRACT In an effort to explore myxobacterial natural product biosynthetic pathways, the draft genome sequence of Cystobacter ferrugineus strain Cbfe23 has been obtained. Analysis of the genome using antiSMASH suggests a multitude of unique natural product biosynthetic pathways. This genome will contribute to the investigation of secondary metabolism in other myxobacterial species.


2015 ◽  
Vol 32 (2) ◽  
pp. 212-229 ◽  
Author(s):  
Lloyd W. Sumner ◽  
Zhentian Lei ◽  
Basil J. Nikolau ◽  
Kazuki Saito

Plant metabolomics has matured and modern plant metabolomics has accelerated gene discoveries and the elucidation of a variety of plant natural product biosynthetic pathways.


2011 ◽  
Vol 7 ◽  
pp. 1622-1635 ◽  
Author(s):  
Jan-Christoph Kehr ◽  
Douglas Gatte Picchi ◽  
Elke Dittmann

Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future.


2020 ◽  
Vol 38 (7) ◽  
pp. 715-728 ◽  
Author(s):  
Muhammad Nazeer Abbasi ◽  
Jun Fu ◽  
Xiaoying Bian ◽  
Hailong Wang ◽  
Youming Zhang ◽  
...  

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