A new bacterial biosynthesis pathway has been discovered to help discover and manufacture new drugs.

Photo from Chi PTing"
The enzymes in these bacteria respond incredibly..When we first observed them, we were confusedWe then had to take great pains to confirm that we believe that these enzyme reactions did occurvan der Donk and his team worked with Tamir Gonen, a professor of biochemistry and physiology at the University of California, Los Angeles, to confirm their findingsvan der Donk team, including the paper's first author, Chi Ting, aims to explore the genome to discover new natural products, potentially useful substances produced by bacteria, a strategy known as genome mining"Genome mining allows you to start looking for compounds that you don't even know what they're going to be," saysvan der DonkMany of our teams are trying to find new antibiotics through genome mining..You're looking for something unusual, we don't know how it's made, and then you try to make it in a friendly organismcells use a special chemical component called amino acids to make proteins, which are the main structures and internal molecular machines of organismsProteins are long chains of 20 different types of amino acids; peptides are shorter chains of amino acidsSome types of bacterial natural products are formed by small peptides modified by chemicals sold on the marketprotein and most peptides are made of ribosomes, a large molecular machine in cells, like a pastry chef in a bakeryAccording to the recipes written in the genes, ribosomes can connect any amino acid sequence together; Other peptide-based natural products are made from a specific set of enzymes that act like a home baker, recusing their favorite recipes--- these enzymes do not follow the template, but constantly create the same type of connections and modifications, resulting in only one natural product"Both approaches are used in the biosynthesis of natural products, " saysvan der DonkNow, we have stumbled upon a new way to characterize both approachesthe researchers made their unexpected discovery when they discovered a cluster of genes in the study of the plant's pseudomonas syringaeThey found that in this gene cluster, one gene carries information about the peptides used by the ribosomes, while the other encodes an enzyme that adds another amino acid to the peptide chainThe pastry chef assembles the dough to make bread, but hands it over to the home baker to complete the preparation"In retrospect, it was just a very smart way of doing things, " saysvan der DonkThere is an enzyme that can have this effect on a pre-existing peptide, which means that today..You can use this peptide as a stent, making natural products again and againthe type of synthesis they found in pseudomonas works in this way because once a new amino acid is added to a pre-existing peptide, it is modified in a series of steps and then destroyed, returning to the initial step of making peptides from ribosomesIn this way, it's a bit like a yeast fermentation agentAs long as it remains active, it doesn't need to be recreated to make every subsequent batch of breadin order to fully describe their natural products and their synthesis, the van der Donk team wanted to better understand its structureHowever, natural product molecules have been shown to be too unstable to use traditional techniquesThe team sought Gonen's help Gonen Labs recently used a cutting-edge technique --- electroscopy of microcrystals of fast-frozen purified substances to determine the structure of small molecules "Once you make a natural product, now you need to figure out what it is.. Our collaborators wanted to demonstrate the usefulness of this approach in creating molecules of unknown natural origin For both labs, this is a real win-win situation I think the whole natural product research community probably wants to start using this technology Given that van der Donk and his team are aware of the existence of this alternative synthesis pathway, they have found other examples of similar mechanisms, including anti-tumor compounds produced by soil bacteria In addition to expanding the ability to identify gene clusters that make promising natural products, the researchers were excited to discover new ways to use this alternative synthesis pathway "We're also excited about how to use it in synthetic biology, " says van der Donk This is because the cost of making a natural product, that is, the amount of resources, is quite low here You make peptides, some enzymes, and then you produce an anti-tumor compound.. There are many people who are interested in modifying bacteria to have anti-cancer activity, which is a relatively easy outcome for bacteria to make molecules for you "
original source: Chi P Ting et al Use of a scaffold in the biosynthesis of amino acid-derived natural products Science, 2019, doi:10.1126/science.newly discovery biosynthetic in disease-type for drug discovery and production Original title: Science: Discovering a new bacterial biosynthesis pathway that promises to discover and manufacture new drugs