Precursors for Aliphatic Penicillins<sup>1</sup>

Thorn, J. A.; Johnson, Marvin J.

doi:10.1021/ja01161a049

Cited by 18 publications

(5 citation statements)

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“…The formation of these side products occurs because isopenicillin N acyltransferase is able to accept many CoA activated fatty acids as a donor in the acyltransferase reaction with isopenicillin N [1,39,43]. The results presented here show that PCL also may have been recruited for the penicillin G biosynthesis.…”

Section: Discussionmentioning

confidence: 69%

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Characterization of a phenylacetate–CoA ligase from Penicillium chrysogenum

Koetsier

Jekel

Berg

et al. 2008

Biochemical Journal

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Enzymatic activation of PAA (phenylacetic acid) to phenylacetyl-CoA is an important step in the biosynthesis of the beta-lactam antibiotic penicillin G by the fungus Penicillium chrysogenum. CoA esters of PAA and POA (phenoxyacetic acid) act as acyl donors in the exchange of the aminoadipyl side chain of isopenicillin N to produce penicillin G or penicillin V. The phl gene, encoding a PCL (phenylacetate-CoA ligase), was cloned in Escherichia coli as a maltose-binding protein fusion and the biochemical properties of the enzyme were characterized. The recombinant fusion protein converted PAA into phenylacetyl-CoA in an ATP- and magnesium-dependent reaction. PCL could also activate POA, but the catalytic efficiency of the enzyme was rather low with k(cat)/K(m) values of 0.23+/-0.06 and 7.8+/-1.2 mM(-1).s(-1) for PAA and POA respectively. Surprisingly, PCL was very efficient in catalysing the conversion of trans-cinnamic acids to the corresponding CoA thioesters [k(cat)/K(m)=(3.1+/-0.4)x10(2) mM(-1).s(-1) for trans-cinnamic acid]. Of all the substrates screened, medium-chain fatty acids, which also occur as the side chains of the natural penicillins F, DF, H and K, were the best substrates for PCL. The high preference for fatty acids could be explained by a homology model of PCL that was constructed on the basis of sequence similarity with the Japanese firefly luciferase. The results suggest that PCL has evolved from a fatty-acid-activating ancestral enzyme that may have been involved in the beta-oxidation of fatty acids.

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Section: Discussionmentioning

confidence: 69%

“…strain Q176) were shown to produce a mixture of these penicillins when no (additional) PAA was supplied in the feed [42]. It was shown that in a defined medium without any PAA, penicillin G is not produced, and the addition of medium or long chain fatty acids results in higher levels of penicillin K, F and DF [25,43] .…”

Section: Discussionmentioning

confidence: 99%

Characterization of a phenylacetate–CoA ligase from Penicillium chrysogenum

Koetsier

Jekel

Berg

et al. 2008

Biochemical Journal

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“…When sufficient amounts of phenylacetic acid (or related compound) were added, all of the penicillin formed was benzylpeni~illin,~~ while when no precursor was added a variety of penicillins were formed. 33 The balance of ingredients was found to be important, since special problems were encountered in determining the amounts of K, S, P, Mg, Fe, Zn, Mn, and Cu required for maximum penicillin yield^.^^,^^ It is of interest to note that the same ingredients were found essential when the cultures were grown in surface culture^.^^,^^ H~c k e n h u l l~~ has pointed out the chemical relationships between the cornsteep liquor-lactose media and the chemically defined media; some of his findings are summarized in TABLE 3. It is evident that those studying the production of benzylpenicillin in chemically defined media have tried to include in their media as many of the possibly "useful" ingredients found in the cornsteep liquor as is feasible.…”

Section: Referencesmentioning

confidence: 99%

Chemically Defined Media for Antibiotic Production

Perlman

1966

Annals of the New York Academy of Sciences

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“…Over the past two decades, the popularity of single photon experiments in undergraduate laboratory courses has increased dramatically. This is a result of technological advances and the effort of a dedicated group of researchers who have developed experiments investigating basic principles of quantum mechanics that are suitable for undergraduates to perform [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%