Introduction of prnA, the halogenase gene from pyrrolnitrin biosynthesis, into Streptomyces coeruleorubidus resulted in efficient in situ chlorination of the uridyl peptide antibotic pacidamycin. The ...installed chlorine provided a selectably functionalizable handle enabling synthetic modification of the natural product using mild cross-coupling conditions in crude aqueous extracts of the culture broth.
Serine carboxypeptidase-like (SCPL) proteins have recently emerged as a new group of plant acyltransferases. These enzymes share homology with peptidases but lack protease activity and instead are ...able to acylate natural products. Several SCPL acyltransferases have been characterized to date from dicots, including an enzyme required for the synthesis of glucose polyesters that may contribute to insect resistance in wild tomato (Solanum pennellii) and enzymes required for the synthesis of sinapate esters associated with UV protection in Arabidopsis thaliana. In our earlier genetic analysis, we identified the Saponin-deficient 7 (Sad7) locus as being required for the synthesis of antimicrobial triterpene glycosides (avenacins) and for broad-spectrum disease resistance in diploid oat (Avena strigosa). Here, we report on the cloning of Sad7 and show that this gene encodes a functional SCPL acyltransferase, SCPL1, that is able to catalyze the synthesis of both N-methyl anthraniloyl- and benzoyl-derivatized forms of avenacin. Sad7 forms part of an operon-like gene cluster for avenacin synthesis. Oat SCPL1 (SAD7) is the founder member of a subfamily of monocot-specific SCPL proteins that includes predicted proteins from rice (Oryza sativa) and other grasses with potential roles in secondary metabolism and plant defense.
A tin(II) chloride-mediated short, efficient, and practical regioselective synthesis of biheterocyclic 5,6-dihydro-quinazolino4,3-bquinazolin-8-ones with three-point diversity is reported. A one-step ...reductive transformation of 2-(2-nitrophenyl)-3H-quinazolin-4-one in various alcohols furnished the desired tetracyclic product in good yields with high purity.
A convenient and high yielding procedure for the Suzuki-Miyaura cross-coupling of unprotected bromo- and chlorotryptophans in water provides fluorescent aryltryptophans.
Rapamycin is a drug with several important clinical uses. Its complex structure means that total synthesis of this natural product and its analogues is demanding and lengthy. A more expeditious ...approach is to utilise biosynthesis to enable the generation of otherwise synthetically intractable analogues. In order to achieve this, rules governing biosynthetic precursor substrate preference must be established. Through determining these rules and synthesising and administering suitable substrate precursors, we demonstrate the first generation of fluorinated rapamycin analogues. Here we report the generation of six new fluororapamycins.
A one-pot biotransformation for the generation of a series of
l-aminotryptophans using tryptophan synthase-containing bacterial cell free extract is reported. The extract can be freeze-dried and ...stored without appreciable loss of activity.
A one-pot biotransformation for the generation of a series of
l-aminotryptophans using a readily prepared protein extract containing tryptophan synthase is reported. The extract exhibits remarkable stability upon freeze-drying, and may be stored and used for long periods after its preparation without significant loss of activity.
Synthesis and potent neuroleptic activity of a novel 1,2,3,4,6,6a,7,11b,12,12a-decahydropyrazino2′,1′:6,1pyrido3,4-
bindole derivative having
D
1,
D
2, and 5-HT
2A receptor blocking activity (p
K
i ...(5-HT
2A)/p
K
i (
D
2)
=
1.42) is reported.
In our pursuit to prepare a potent antipsychotic compound, a novel 1,2,3,4,6,6a,7,11b,12,12a-decahydropyrazino2′,1′:6,1pyrido3,4-
bindole derivative was synthesized which incorporates the butyrophenone substructure twice. This molecule has shown
D
1,
D
2 and 5-HT
2A receptor blocking activity where the ratio p
K
i (5-HT
2A) to p
K
i (
D
2) is 1.42 better than risperidone (1.15). It blocks amphetamine induced hyperactivity/stereotypy and secondary conditioned avoidance responses in rodents at lower doses than those required for the neuroleptic drugs haloperidol and centbutindole (biriperone).
Plants produce a huge array of specialized metabolites that have important functions in defense against biotic and abiotic stresses. Many of these compounds are glycosylated by family 1 ...glycosyltransferases (GTs). Oats (Avena spp.) make root-derived antimicrobial triterpenes (avenacins) that provide protection against soil-borne diseases. The ability to synthesize avenacins has evolved since the divergence of oats from other cereals and grasses. The major avenacin, A-1, is acylated with N-methylanthranilic acid. Previously, we have cloned and characterized three genes for avenacin synthesis (for the triterpene synthase SAD1, a triterpene-modifying cytochrome P450 SAD2, and the serine carboxypeptidase-like acyl transferase SAD7), which form part of a biosynthetic gene cluster. Here, we identify a fourth member of this gene cluster encoding a GT belonging to clade L of family 1 (UGT74H5), and show that this enzyme is an N-methylanthranilic acid O-glucosyltransferase implicated in the synthesis of avenacin A-1. Two other closely related family 1 GTs (UGT74H6 and UGT74H7) are also expressed in oat roots. One of these (UGT74H6) is able to glucosylate both N-methylanthranilic acid and benzoic acid, whereas the function of the other (UGT74H7) remains unknown. Our investigations indicate that UGT74H5 is likely to be key for the generation of the activated acyl donor used by SAD7 in the synthesis of the major avenacin, A-1, whereas UGT74H6 may contribute to the synthesis of other forms of avenacin that are acylated with benzoic acid.
Background: Glycosyltransferases (GTs) have important functions in plant secondary metabolism.
Results: A gene encoding an N-methylanthranilic acid O-glucosyltransferase forms part of a biosynthetic cluster for the synthesis of acylated defense compounds in oat.
Conclusion: This GT synthesizes the activated acyl donor required for triterpene acylation.
Significance: These findings open up new opportunities for metabolic engineering for disease control.
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