To discover new compounds with antibacterial activity against drug-resistant pathogens, we developed a library of Streptomyces sp. Mangrove-associated microorganisms, especially actinomycetes, have been demonstrated to be an important source of antibiotics 20. In addition to their fascinating structures, these compounds formed through nonenzymatic reactions also exhibit potent biological activities 15, 16, 17. Dibohemamines A−C are formed via the spontaneous dimerization of bohemamines and formaldehyde 17. Aeruginaldehyde and different aminopyrrolnitrin derivatives undergo an abiotic Pictet−Spengler reaction to generate pyonitrins A−D 19. Discoipyrrole A is formed from three starting metabolites, 4-hydroxysattabacin, anthranilic acid, and 4-hydroxybenzaldehyde, under mild conditions 18. A growing number of natural products possessing unprecedented chimeric frameworks formed through spontaneous chemical reactions have been discovered, such as discoipyrroles 15, pyonitrins 16, and dibohemamines 17. Moreover, chemists have constructed these complex skeletons using efficient synthesis strategies 11, 12, 13, 14. The enzymatic catalysis of these reactions has attracted great attention 8, 9, 10. Chimeric natural products comprise a group of structurally novel and diverse compounds that are formed from two or more types of primary or secondary metabolites through well-known reactions such as cycloaddition, condensation, and esterification. However, the biosynthetic processes of some extremely complex natural products are still unclear, since some involve spontaneous nonenzymatic reactions for their formation. Most information related to the biosynthesis of secondary metabolites can be traced back to the genome sequences 3, 4, 5, 6, 7. Researchers use genomic sequence information to identify and annotate biosynthetic gene clusters whose gene products are involved in the biosynthesis of novel natural product scaffolds. Research methods at the gene and enzyme levels, such as genome mining and heterologous expression, are increasingly being used to discover novel natural products and elucidate their biosynthetic pathways. Various microbial natural products have recently attracted much attention from researchers in the areas of biosynthesis and chemical synthesis. As an important source of antibiotics, microorganisms have great potential to produce new compounds effective against drug-resistant bacteria 2. To address this looming problem, antibiotics with new structures and novel mechanisms of action are urgently needed. This work paves the way for understanding the nonenzymatic formation of complex natural products and using it to synthesize natural product derivatives.Īntibiotic resistance has become one of the biggest threats to public health 1. The synthetic compounds, chimedermycins L and M, and sekgranaticin B, show potent antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. This strategy was further developed to efficiently synthesize analogues for biological activity studies. The formation of these compounds features some key nonenzymatic steps, which inspired us to construct complex polycyclic skeletons via three efficient one-step reactions under mild conditions. Herein, we report eight chimeric medermycin-type natural products with unusual polycyclic skeletons. The biosynthesis of this family of natural products has been studied, and new skeletons related to medermycin have rarely been reported until recently. Neither ILO nor WHO nor the European Commission shall be responsible for the interpretation and use of the information contained in this material.Medermycin, produced by Streptomyces species, represents a family of antibiotics with significant activity against Gram-positive pathogens. The published material is being distributed without warranty of any kind, either expressed or implied. The substance is mildly irritating to the eyes.Įvaporation at 20☌ is negligible a nuisance-causing concentration of airborne particles can, however, be reached quickly when dispersed, especially if powdered.Įffects of long-term or repeated exposureĪll rights reserved. The substance can be absorbed into the body by ingestion. With the financial assistance of the European Commission. Prepared by an international group of experts on behalf of ILO and WHO,
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