Antibacterial Pentacyclic Polyketides from a Soil-Derived <i>Streptomyces</i>

Yuan, Jie; Wang, Li; Ren, Jinqiu; Huang, Jianping; Yu, Mingming; Tang, Jun; Yan, Yijun; Yang, Jing; Huang, Sheng‐Xiong

doi:10.1021/acs.jnatprod.0c00161

Cited by 16 publications

(37 citation statements)

References 22 publications

(46 reference statements)

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“…Phenyltetracenoid polyketides, including fasamycins, − formicamycins, ,, naphthacemycins, − streptovertimycins, and accramycins, , are a class of Streptomyces metabolites possessing a partially reduced 1-phenyltetracene core. They have attracted attention due to their activity against antibiotic-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). − ,− Some also inhibited Poly(ADP-ribose) polymerase-1 (PARP1) and protein tyrosine phosphatase-1B (PTP-1B) . More than 90 members of this class of polyketides have been reported. − They can be categorized into four subclasses according to their structures, i.e., fasamycin-type, formicamycin-type, naphthacemycin-A-type, and naphthacemycin-C-type, as represented by fasamycin A, formicamycin A, naphthacemycin A 1 , and naphthacemycin C 1 , respectively (Figure ).…”

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Antibacterial and Cytotoxic Phenyltetracenoid Polyketides from Streptomyces morookaense

et al. 2021

J. Nat. Prod.

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Formicapyridine-type racemates, streptovertidines A (1) and B (2), a 7,24-seco-fasamycin, streptovertidione (3), and the fasamycin-type streptovertimycins I−T (4−15), together with 13 known fasamycin congeners (16−28), were isolated from soilderived Streptomyces morookaense SC1169. Their structures were elucidated by extensive spectroscopic analysis and theoretical computations of ECD spectra. The fasamycin-type compounds 5, 8−12, 14, and 15 exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC: 1.25−10.0 μg/mL). All isolates, except 3, 4, 10, and 24, displayed cytotoxicity against at least one of the human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC 50 < 10.0 μM), of which some were also cytotoxic to the noncancerous Vero cells. Taken together, the activity data demonstrated that the fasamycin-type compounds were more selective to the tested bacteria over the mammalian cells. Structure−activity relationship analysis suggested that chlorination at C-2 in antibacterial fasamycin-type compounds improves the activity and selectivity to the bacteria. Theoretical simulations of reaction paths and chemical reactions for conversion of 3 to 1 were carried out and supported that the pyridine ring formation in formicapyridines proceeds nonenzymatically via 1,5-dicarbonyl condensation with ammonia.

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Antibacterial and Cytotoxic Phenyltetracenoid Polyketides from Streptomyces morookaense

et al. 2021

J. Nat. Prod.

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“…Taken together, through in vitro enzymatic reactions, we unveiled two halogenases that can specifically catalyze the mono or double halogenation of fasamycins at C-2 or C- 15 and H (2). 17 The axial chirality at C 6 −C 7 of 3 was defined as a P configuration by comparing its ECD curve (Figure 5) with that of 2. 1 Fasamycin T (4) possessed the molecular formula of − , 505.1060), one chlorine atom more than that of compound 1.…”

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Expanding the Chemical Diversity of Fasamycin Via Genome Mining and Biocatalysis

et al. 2022

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Genome mining and biocatalytic modification of chemical structures are critical methods to develop new antibiotics. In this study, eight new fasamycins (3, 4, 6, and 8−12) along with five known analogues (1, 2, 5, 7, and 13) were obtained by the overexpression of two phosphopantetheinyl transferases (PPtases) in Streptomyces kanamyceticus and biocatalytic transformation with two halogenases. These new compounds displayed significant activity against Staphylococcus aureus and Bacillus subtilis, in particular, C-29-methyl and C-2/C-22-halogen derivatives. This study increases the chemical diversity of bioactive fasamycin derivatives and provides useful halogenation tools for engineering their scaffolds.

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“…Formicamycins ( Figure 4 ), pentacyclic type II PKS products from Streptomyces formicae (a strain isolated from the tree-associated Tetraponera ants which shows an impressive secondary metabolism potential [ 93 ]), show potent activity against Gram-positive pathogens without apparent generation of spontaneous resistance [ 94 , 95 , 96 , 97 ]. Formicamycins have also been recently isolated from a soil Streptomyces strain [ 98 ]. The degree of specificity and co-evolution in the ant-actinobacteria associations has been a matter of debate [ 80 , 99 , 100 ], although ants from the Attini tribe (leaf-cutter ants) have evolved specific structures to host Pseudonocardia spp.…”

Section: Insect-associated Bacteriamentioning

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Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

Santos‐Aberturas

Vior

2022

Antibiotics

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Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis has brought a considerable amount of attention to the study of previously neglected bacterial sources of secondary metabolites. The development and application of new screening, sequencing, genetic manipulation, cultivation and bioinformatic techniques have revealed several other groups of bacteria as producers of striking chemical novelty. Biosynthetic machineries evolved from independent taxonomic origins and under completely different ecological requirements and selective pressures are responsible for these structural innovations. In this review, we summarize the most important discoveries related to secondary metabolites from alternative bacterial sources, trying to provide the reader with a broad perspective on how technical novelties have facilitated the access to the bacterial metabolic dark matter.

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Antibacterial Pentacyclic Polyketides from a Soil-Derived Streptomyces

Cited by 16 publications

References 22 publications

Antibacterial and Cytotoxic Phenyltetracenoid Polyketides from Streptomyces morookaense

Antibacterial and Cytotoxic Phenyltetracenoid Polyketides from Streptomyces morookaense

Expanding the Chemical Diversity of Fasamycin Via Genome Mining and Biocatalysis

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

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