Timing of the Δ10,12-Δ11,13 Double Bond Migration During Ansamitocin Biosynthesis in Actinosynnema pretiosum

Taft, Florian; Brünjes, Marco; Knobloch, Tobias; Floss, Heinz G.; Kirschning, Andreas

doi:10.1021/ja8088923

Cited by 63 publications

(53 citation statements)

References 20 publications

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“…Likewise, the double bonds D 25, 27 and D 11, 12 appear to have changed position relative to their locations in regular PKS/NRPS systems, although exceptions to this have recently been described. [21][22][23][24] Analysis of the corallopyronin A biosynthetic gene cluster Feeding experiments showed that the core structure of corallopyronin A is the product of a mixed PKS/NRPS biosynthetic machinery. Investigations with 13 C-labelled SAM, as well as the positions of the corresponding methyl functionalities (i.e., aor b-branching or ÀOCH 3 ) in the molecule, clearly showed that methyl and methoxy groups are incorporated by two mechanisms: from SAM dependent by MTs and by the successive action of a b-branching cassette.…”

Section: Wwwchembiochemorgmentioning

confidence: 99%

Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

et al. 2010

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Corallopyronin A is a myxobacterial compound with potent antibacterial activity. Feeding experiments with labelled precursors resulted in the deduction of all biosynthetic building blocks for corallopyronin A and revealed an unusual feature of this metabolite: its biosynthesis from two chains, one solely PKS-derived and the other NRPS/PKS-derived. The starter molecule is believed to be carbonic acid or its monomethyl ester. The putative corallopyronin A biosynthetic gene cluster is a trans-AT-type mixed PKS/NRPS gene cluster, containing a beta-branching cassette. Striking features of this gene cluster are a NRPS-like adenylation domain that is part of a PKS-type module and is believed to be responsible for glycine incorporation, as well as split modules with individual domains occurring on different genes. It is suggested that CorB is a trans-acting ketosynthase and it is proposed that it catalyses the Claisen condensation responsible for the interconnection of the two chains. Additionally, the stereochemistry of corallopyronin A was deduced by a combination of a modified Mosher's method and ozonolysis with subsequent chiral GC analyses.

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Section: Wwwchembiochemorgmentioning

confidence: 99%

Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

et al. 2010

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“…One is 4,5-C=C moiety in geldanamcyin [8], in which the ER domain in module 6 is apparently functional. Another is that, even though asm DH3 seemed functional, 10,12 double bond migrates to 11,13 in ansamitocin P3 [88]. Despite some shortcomings that can not be overcome in near future, the actually elucidated structures will not deviate too far from the predicted ones.…”

Section: Non-colinearitymentioning

confidence: 95%

Biosynthetic Pathways and Engineering for Bioactive Natural Products

Wei¹,

Wang²,

Shang³

2010

COC

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Natural products synthesized by polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and the hybrid PKS-NRPS have been valuable sources for bioactive compounds due to their structural diversity and wide variety of biological activities. Progresses in the biosynthetic study of natural products in recent years reinvigorate the hope of discovering new compounds for clinical use. This review focuses on the elucidation of biosynthetic pathways of PKS and NRPS, the more "abnormal" biosynthetic reactions, the manipulation of gene cluster to increase product yields, as well as the catalytic applications of the enzymes originated from secondary metabolism. Genome mining or key regulatory gene activation to obtain "silent" gene cluster and the progresses on using sequencing data to predict the generation of natural products are also summarized.

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“…Key steps are the introduction of the stereogenic center at C-14 by an Evans alkylation and a phosphonate-based olefination using α-methoxy SNAC ester 68. 41 We demonstrated that mutasynthesis is ideally suited to the synthesis of highly potent ansamitocins, making it a showcase for combining the use of different blocked mutants with chemical synthesis. Several hybrid concepts were tested and allowed a large number of analogues of this class of structurally complex secondary metabolites to be generated.…”

Section: Blocked Mutants As Tools For Biosynthetic Studies Of Ansamitmentioning

confidence: 99%

Ansamitocin Libraries by Combining Mutasynthesis with Chemical Synthesis; A New Version of Total Synthesis

Taft¹,

Eichner²,

Knobloch³

et al. 2012

Synlett

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Blocked mutants of Actinosynnema pretiosum, the producer of the highly cytotoxic antitumor agent ansamitocin, serve as powerful tools that allow synthetic chemists to generate natural product libraries. The power of this approach can be dramatically expanded when mutasynthesis is combined with chemical synthesis. This report provides illustrative examples of the application of this strategy to produce libraries based on the ansamycin antibiotics.

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Timing of the Δ_10,12-Δ_11,13 Double Bond Migration During Ansamitocin Biosynthesis in Actinosynnema pretiosum

Cited by 63 publications

References 20 publications

Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

Biosynthetic Pathways and Engineering for Bioactive Natural Products

Ansamitocin Libraries by Combining Mutasynthesis with Chemical Synthesis; A New Version of Total Synthesis

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