Modern mass spectrometry for synthetic biology and structure-based discovery of natural products

Henke, Matthew T.; Kelleher, Neil L.

doi:10.1039/c6np00024j

Cited by 56 publications

(53 citation statements)

References 67 publications

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“…The crude mixture is then fractionated, based on novelty, as compared to the historic DAS NP collection, according to the analytical evaluation. The fractions are re‐assessed for unique structural features, subsequently purified, and tested for bioactivity . At CAS, the focus on a bioactivity‐based tactic has proven fruitful, albeit lengthy, in identifying agrochemically relevant NPs of interest .…”

Section: Strategies To Identify Natural Productsmentioning

confidence: 99%

“…The fractions are re-assessed for unique structural features, subsequently purified, and tested for bioactivity. 46 At CAS, the focus on a bioactivity-based tactic has proven fruitful, albeit lengthy, in identifying agrochemically relevant NPs of interest. 21,31,40,42,47 The specific workflow and screening cascade utilized currently is illustrated in Fig.…”

Section: Strategies To Identify Natural Productsmentioning

confidence: 99%

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Natural products: a strategic lead generation approach in crop protection discovery

Lorsbach

Sparks

Cicchillo

et al. 2019

Pest Management Science

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With the anticipated population growth in the coming decades, the changing regulatory environment, and the continued emergence of resistance to commercial pesticides, there is a constant need to discover new lead chemistries with novel modes of action. We have established a portfolio of approaches to accelerate lead generation. One of these approaches capitalizes on the rich bioactivity of natural products (NPs), highlighted by the numerous examples of NP‐based crop protection compounds. Within Corteva Agriscience and the affiliated preceding companies, NPs have been a fruitful approach, for nearly three decades, to identifying and bringing to the market crop protection products inspired by or originating from NPs, . Included in these NP‐based crop protection products are the spinosyns family of insecticides, and those from more recent areas of NP‐based fungicidal chemistry, as highlighted in this perspective. © 2019 Society of Chemical Industry

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Section: Strategies To Identify Natural Productsmentioning

confidence: 99%

Section: Strategies To Identify Natural Productsmentioning

confidence: 99%

Natural products: a strategic lead generation approach in crop protection discovery

Lorsbach

Sparks

Cicchillo

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

show abstract

“…The relationships between GCFs and MFs can be utilized to aid in genome mining of unsequenced organisms. A plethora of MS/MS-based computational tools such as NRPquest and RiPPquest have been developed, which were reviewed elsewhere [57,58]. Although most of these computational tools are limited to the analysis of peptide natural products, it can be expected that such MS/MS based approaches will be extended to other natural products in the future.…”

Section: High-throughput Product Detectionmentioning

confidence: 99%

Breaking the silence: new strategies for discovering novel natural products

Ren

Wang

Zhao

2017

Current Opinion in Biotechnology

102

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Natural products have been a prolific source of antibacterial and anticancer drugs for decades. One of the major challenges in natural product discovery is that the vast majority of natural product biosynthetic gene clusters (BGCs) have not been characterized, partially due to the fact that they are either transcriptionally silent or expressed at very low levels under standard laboratory conditions. Here we describe the strategies developed in recent years (mostly between 2014–2016) for activating silent BGCs. These strategies can be broadly divided into two categories: approaches in native hosts and approaches in heterologous hosts. In addition, we briefly discuss recent advances in developing new computational tools for identification and characterization of BGCs and high-throughput methods for detection of natural products.

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“…Recently, mass spectrometry (MS) has been recognized as a tool yielding huge potential for high‐throughput discovery of lead compounds from HM . MS is highly critical to drug discovery and preclinical development needs.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry‐driven drug discovery for development of herbal medicine

Zhang

Sun

Wang

2016

Mass Spectrometry Reviews

139

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Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes.

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Modern mass spectrometry for synthetic biology and structure-based discovery of natural products

Cited by 56 publications

References 67 publications

Natural products: a strategic lead generation approach in crop protection discovery

Natural products: a strategic lead generation approach in crop protection discovery

Breaking the silence: new strategies for discovering novel natural products

Mass spectrometry‐driven drug discovery for development of herbal medicine

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