Assigning the stereochemical structures of aurantinin A and B with the assistance of biosynthetic investigations

Wang, Dacheng; Li, Pengwei; Jia, Yan; Mao, Huijin; Liu, Lilu; Wang, Min; Chen, Meng; Ye, Tao; Chen, Yihua

doi:10.1039/d2qo01251k

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Assignment of the two enantiomers were performed by comparing their CD spectra with the calculated electronic circular dichroism (ECD) spectra of d-M-283-SNAC and l-M-283-SNAC (Additional file 1, Fig. S22), which were carried out with Conflex 7.0a, Gaussian9, and Shermo 2.3 as described [49].…”

Section: Chemical Syntheses and Separation Of D/l-m-283-snacmentioning

confidence: 99%

Human-associated bacteria adopt an unusual route for synthesizing 3-acetylated tetramates for environmental adaptation

et al. 2023

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Background Tetramates or tetramic acid-containing compounds (TACs) are a group of bioactive natural products featuring a pyrrolidine-2,4-dione ring acknowledged being closed via Dieckmann cyclization. The cariogenic Streptococcus mutans strains bearing a muc biosynthetic gene cluster (BGC) can synthesize mutanocyclin (MUC), a 3-acetylated TAC that can inhibit both leukocyte chemotaxis and filamentous development in Candida albicans. Some strains can also accumulate reutericyclins (RTCs), the intermediates of MUC biosynthesis with antibacterial activities. However, the formation mechanism of the pyrrolidine-2,4-dione ring of MUC and the distribution of muc-like BGCs along with their ecological functions has not been explored extensively. Results We demonstrated that a key intermediate of MUC biosynthesis, M-307, is installed by a hybrid nonribosomal peptide synthetase-polyketide synthase assembly line and its pyrrolidine-2,4-dione ring is closed via an unprecedented lactam bond formation style. Subsequent C-3 acetylation will convert M-307 to RTCs, which is then hydrolyzed by a deacylase, MucF, to remove the N-1 fatty acyl appendage to generate MUC. Distribution analysis showed that the muc-like BGCs distribute predominantly in human-associated bacteria. Interestingly, most of the muc-like BGCs possessing a mucF gene were isolated from human or livestock directly, indicating their involvement in alleviating the host’s immune attacks by synthesizing MUC; while those BGCs lacking mucF gene distribute mainly in bacteria from fermented products, suggesting that they tend to synthesize RTCs to compete with neighboring bacteria. It is noteworthy that many bacteria in the same habitats (e.g., the oral cavity) lack the muc-like BGC, but possess functional MucF homologues to “detoxify” RTCs to MUC, including several competitive bacteria of S. mutans. We also comparably studied the distribution of TAS1, a fungal enzyme responsible for the production of phytotoxic tenuazonic acids (TeAs), a class of 3-acetylated TACs with similar structure but distinct biosynthetic mechanism to MUC, and found that it mainly exists in plants or crops. Conclusions The in vivo and in vitro experiments revealed that the pyrrolidine-2,4-dione ring of MUC is closed via lactam bond formation, which may be adopted by many TACs without 3-acyl decorations. Besides, we found that muc-like BGCs are widespread in human-associated bacteria and their shapes and main products can be influenced by the habitat environment and vice versa. By comparing with TeAs, we provided thought-provoking insights into how ecological and evolutionary forces drive bacteria and fungi to construct a common 3-acetylated pyrrolidine-2,4-dione core through different routes, and how the biosynthetic processes are delicately controlled to generate diverse 3-acetylated TACs for environmental adaptation.

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Section: Chemical Syntheses and Separation Of D/l-m-283-snacmentioning

confidence: 99%

Human-associated bacteria adopt an unusual route for synthesizing 3-acetylated tetramates for environmental adaptation

et al. 2023

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Reprogramming of the Aurantinin Polyketide Assembly Line to Synthesize Auritriacids by Excising an Atypical Enoyl‐CoA Hydratase Domain

Wang,

Mao,

Zhao

et al. 2024

Advanced Science

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Modular polyketide synthases (PKSs) are capable of synthesizing diverse natural products with fascinating bioactivities. Canonical enoyl‐CoA hydratases (ECHs) are components of the β‐branching cassette that modifies the polyketide chain by adding a β‐methyl branch. Herein, it is demonstrated that the deletion of an atypical ECHQ domain (featuring a Q280 residue) of Art21, a didomain protein contains an ECHQ domain and a thioesterase (TE) domain, reprograms the polyketide assembly line from synthesizing tetracyclic aurantinins (ARTs) to bicyclic auritriacids (ATAs) with much lower antibacterial activities. Genes encoding the ECHQ‐TE didomain proteins distribute in many PKS gene clusters from different bacteria. Significantly, the ART PKS machinery can be directed to make ARTs, ATAs, or both of them by employing appropriate ECHQ‐TE proteins, implying a great potential for using this reprogramming strategy in polyketide structure diversification.

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Characterization of three succinyl-CoA acyltransferases involved in polyketide chain assembly

Liu

Wang

Chen

et al. 2023

Appl Microbiol Biotechnol

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Assigning the stereochemical structures of aurantinin A and B with the assistance of biosynthetic investigations

Abstract: Aurantinins (ARTs) are a group of antibacterial polyketides featuring a 6/7/8/5-fused tetracyclic ring system and a triene alkyl chain with a carboxylic terminus. Previous studies assigned their planar structures and...

Cited by 3 publications

References 36 publications

Human-associated bacteria adopt an unusual route for synthesizing 3-acetylated tetramates for environmental adaptation

Human-associated bacteria adopt an unusual route for synthesizing 3-acetylated tetramates for environmental adaptation

Reprogramming of the Aurantinin Polyketide Assembly Line to Synthesize Auritriacids by Excising an Atypical Enoyl‐CoA Hydratase Domain

Characterization of three succinyl-CoA acyltransferases involved in polyketide chain assembly

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