The natural productome

Palazzolo, Andrea M. E.; Simons, Claire L. W.; Burke, Martin D.

doi:10.1073/pnas.1706266114

Cited by 23 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…52 Increasing evidence further suggests that natural product chemical space is bounded, 53 enabling consideration of generalized approaches for studying the complete natural productome. 54 An expanded effort is now underway to find the minimal number of building blocks required to access most natural product chemical space. 55 …”

Section: Many Small Molecules Are Inherently Modularmentioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

Self Cite

View full text Add to dashboard Cite

Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

show abstract

Section: Many Small Molecules Are Inherently Modularmentioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…By analogy, a retrospective analysis on the discovery of NPs shows that the NP space is largely limited and the number of fundamentally novel scaffolds discovered from nature is decreasing. 44,45 To overcome such limitations, biosynthesis may combine two unrelated synthetic routes to generate hybrid NPs, for example hybrid PKS-NRPS, 46 terpenoid alkaloids 47 and meroterpenoids. 48 However, the biosynthetic efficiency is limited by the accessible precursors among microorganisms and plants and the available biosynthetic machinery.…”

Section: Pseudo Natural Productsmentioning

confidence: 99%

Guided by evolution: from biology oriented synthesis to pseudo natural products

2020

View full text Add to dashboard Cite

show abstract

“…Given all this impact already, it is exciting to consider that most of the functional potential that small molecules possess likely remains untapped. [6] This is because this class of chemical matter can also perform many frontier functions that have been minimally utilized to date. These include modulating protein-protein interactions, [7] allosterically modifying protein function, [8] acting as prostheses on the molecular scale, [9] serving as next-generation biological probes, [10] enabling miniaturized diagnostics, [11] harvesting sunlight.…”

Section: Introductionmentioning

confidence: 99%

“…Such compounds serve as most of our best medicines, biological probes,c rop protectants,f ood preservatives,a s well as key components in organic materials,d yes,p aints, perfumes,f lavorants,a nd lotions.G iven all this impact already,i ti se xciting to consider that most of the functional potential that small molecules possess likely remains untapped. [6] This is because this class of chemical matter can also perform many frontier functions that have been minimally utilized to date.T hese include modulating protein-protein interactions, [7] allosterically modifying protein function, [8] acting as prostheses on the molecular scale, [9] serving as next-generation biological probes, [10] enabling miniaturized diagnostics, [11] harvesting sunlight, [12] transducing energy, [13] emitting light, [14] initiating self-healing, [15] acting as molecular magnets, [16] acting as redox flow batteries, [17] enabling next generation computing, [18] and superconducting. [19] Harnessing this untapped functional potential on the molecular scale could help address some of the most important problems facing societies today.H owever,t he hand-crafted and thus inherently slow and specialist-dependent process through which most small molecules are still synthesized represents as ignificant bottleneck in such efforts.T he automation of small-molecule synthesis has the potential to eliminate this bottleneck and thereby enable widespread innovation on the molecular scale.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

2018

Self Cite

View full text Add to dashboard Cite

The eighteenth and nineteenth centuries marked a sweeping transition from manual to automated manufacturing on the macroscopic scale. This enabled an unmatched period of human innovation that helped drive the Industrial Revolution. The impact on society was transformative, ultimately yielding substantial improvements in living conditions and lifespan in many parts of the world. During the same time period, the first manual syntheses of organic molecules was achieved. Now, two centuries later, we are poised for an analogous transition from highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of many different types of molecules with the push of a button. Automation of customized small molecule synthesis pathways is already enabling safer, more reproducible, and readily scalable production of specific targets, and general machines now exist for the synthesis of a wide range of different peptides, oligonucleotides, and oligosaccharides. Creating general machines that are similarly capable of making many different types of small molecules on-demand, akin to that which has been achieved on the macroscopic scale with 3D printers, has proven to be substantially more challenging. Yet important progress is being made toward this potentially transformative objective with two complementary approaches: (1) automation of customized synthesis routes to different targets via machines that enable use of many different reactions and starting materials, and (2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these exciting directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale.

show abstract

The natural productome

Cited by 23 publications

References 29 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Guided by evolution: from biology oriented synthesis to pseudo natural products

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

Contact Info

Product

Resources

About