Structure and biosynthesis of novel antibiotics, aurantinins A and B produced by Bacillus aurantinus

Nakagawa, Akira; Konda, Yaeko; Hatano, Akiko; Harigaya, Yoshihiro; Onda, Masayuki; Ōmura, Satoshi

doi:10.1021/jo00246a059

Cited by 19 publications

(21 citation statements)

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“…The isotope labeling pattern of the ART B aglycone is shown as two separate polyketide chains. The C-1 carbon (marked with a light blue star) was previously proposed to originate from the C-1 of acetate 17 ; in this study, we propose it originates from the free carboxyl end of the malonyl starter unit. b Genetic organization of the art gene cluster.…”

Section: Introductionsupporting

confidence: 49%

“…We therefore sought to begin elucidating the biosynthetic pathway by first dissecting C -methyl incorporation patterns of ART. The ART B aglycone contains seven C -methyl groups, five of which are derived from S -adenosyl- l -methionine (SAM) and two from the C-2 of acetate 17 (Fig. 1a ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous feeding experiments showed that that the terminal free carboxylic acid of ART is derived from the C-1 of a cleaved acetate unit 17 , suggesting a possible origin for the free terminal carboxylic acid group by oxidative C–C bond cleavage of the polyketide chain and subsequent hydrolysis. Such oxidative cleavages have been observed in oocydin A and viriditoxin produced by Serratia plymuthica 4Rx13 and Paecilomyces variotii , respectively, where the Baeyer-Villiger monooxygenases (BVMO) OocK and VdtE inserted an oxygen into the polyketide chain between the two carbons of one acetate unit 26 , 27 .…”

Section: Resultsmentioning

confidence: 99%

“…Biosynthetic insight from previous feeding experiments with isotope-labeled precursors suggested that the ART B aglycone is assembled from two unusual polyketide chains: (i) a short chain containing an uncommon tail-to-tail condensation of two acetate units (C-24 to C-27); (ii) a long dicarboxylic acid chain with one of the two carboxyl groups (C-1 carboxyl of ART) derived from the C-1 of an acetate unit (Fig. 1a ) 17 . However, without knowledge of the ART biosynthetic gene cluster it remains unclear how the two ART polyketide chains are assembled and undergo the unusual cyclization and glycosylation processes.…”

Section: Introductionmentioning

confidence: 98%

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Initiating polyketide biosynthesis by on-line methyl esterification

Chen

Tang

et al. 2021

Nat Commun

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Aurantinins (ARTs) are antibacterial polyketides featuring a unique 6/7/8/5-fused tetracyclic ring system and a triene side chain with a carboxyl terminus. Here we identify the art gene cluster and dissect ART’s C-methyl incorporation patterns to study its biosynthesis. During this process, an apparently redundant methyltransferase Art28 was characterized as a malonyl-acyl carrier protein O-methyltransferase, which represents an unusual on-line methyl esterification initiation strategy for polyketide biosynthesis. The methyl ester bond introduced by Art28 is kept until the last step of ART biosynthesis, in which it is hydrolyzed by Art9 to convert inactive ART 9B to active ART B. The cryptic reactions catalyzed by Art28 and Art9 represent a protecting group biosynthetic logic to render the ART carboxyl terminus inert to unwanted side reactions and to protect producing organisms from toxic ART intermediates. Further analyses revealed a wide distribution of this initiation strategy for polyketide biosynthesis in various bacteria.

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Section: Introductionsupporting

confidence: 49%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Initiating polyketide biosynthesis by on-line methyl esterification

Chen

Tang

et al. 2021

Nat Commun

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“…6-Deoxy-3-ketohexoses are also no typical building blocks produced by bacteria. There exist only a few examples for secondary metabolites containing a 6-desoxy-3-keto-ribo-hexopyranoside: Aurantinin B [18] produced by Bacillus aurantinus and datiscoside [19] isolated from dried twigs of Datisca glomerata. Admittedly, aurantinin B is β-linked and datiscoside contains the α--form while the sugar part of orsellides A (1) and B (2) is a methyl 6-deoxy-3-keto-α--ribo-hexopyranoside.…”

Section: Discussionmentioning

confidence: 99%

Orsellides A–E: An Example for 6‐Deoxyhexose Derivatives Produced by Fungi

Schlörke

Zeeck

2006

Eur J Org Chem

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The antibacterial orsellides A–E (1–5), novel esters consisting of orsellinic acid (6) and a 6‐deoxyhexose, were isolated from Chaetomium sp. (strain Gö 100/9) together with the known metabolites globosumones A (7) and B (8). The structures of the new compounds were elucidated by detailed spectroscopic analysis. The biosynthesis of these metabolites was studied by feeding 13C‐labelled precursors to growing cultures of strain Gö 100/9. The sugar moieties of the orsellides A–E (1–5) as well as the side chains of globosumones A (7) and B (8) originate from carbohydrate intermediates. Thus, the orsellides are rare examples for fungal metabolites containing deoxyhexose building blocks that are normally characteristic for bacterial secondary metabolites. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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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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Structure and biosynthesis of novel antibiotics, aurantinins A and B produced by Bacillus aurantinus

Cited by 19 publications

References 0 publications

Initiating polyketide biosynthesis by on-line methyl esterification

Initiating polyketide biosynthesis by on-line methyl esterification

Orsellides A–E: An Example for 6‐Deoxyhexose Derivatives Produced by Fungi

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

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