Biosynthetic intermediates, chemical

Type II PKSs such as the bacterial aromatic PKSs are comprised of several mono-or di-domain proteins. Although little is known about the interactions among these proteins, and the relevance of these interactions to enzyme function and selectivity, such interactions are presumably important, given the extremely high lability of the inferred biosynthetic intermediates in these pathways. More recently, protein chemical studies and kinetic analysis have provided evidence for interactions between the ACP and the rest of the minimal PKS, as well as between the auxiliary subunits and the minimal PKS [23,24],... 

After the structural study of copper-complex of BLM by the chemical and spec-trometric methods described above, the structure of P-3 A copper-complex, a biosynthetic intermediate of BLM (see II-7) was clarified by X-ray crystallographic analysis supplemented with chemical studies27). The structure is schematically shown in Fig. 17. 

The (Z)-l-HETCA-CoA isomers would chemically racemize at C-4 and thus reduction of only the erythro isomer would produce HTCA or its CoA derivative with the correct stereochemistry at C-4 and C-5. Retaining the CoA portion of the molecule as indicated in Figure 4 would produce an activated carboxylic acid that could be used for the incorporation of HTCA into the final methanofuran. The biosynthetic intermediates, erythro-HPTCA, threo-WVTCh, erythro-VTCh, and threo-VTCh were each identified in cell extracts of Methanococcus vannidii, M. thermophilia strain TM-1, and M. thermoautotrophicus, indicating the widespread occurrence of this pathway in the methanogens. 

Recent results" have shown that only (—)-erysodienone, which has the (5S)-chirality of the natural alkaloids, is a precursor for erythraline (103) and a- and -erythroidine (106). The conversion of (S)-N-norprotosinomenine (100) into (5S)-erysodienone (102), it is apparent, involves, formally at least, an inversion of chirality. However, the chirality of (100) may well be lost in vivo for it was found that the biosynthetic intermediate (101) prepared by chemical reduction from chiral erysodienone underwent very rapid racemization at room temperature. 

Although these strategies of mutasynthesis, precusor-directed biosynthesis, and biotansformation have been discussed separately, one of their mam strengths lies in the way in which they can be overlapped and can complement each other. Mutants can provide novel analogs or biosynthetic intermediates, which can be fed in a rational manner to other organisms to provide further chemical modification, or they themselves can be fed other precursors. 

Nicotine was isolated by Posselt and Reimann in 1828 [1], and subsequently the chemical structure was clarified [2-4]. As described later, the pyridine ring of nicotine is derived from nicotinic acid, which is biosynthesized from aspartic acid. Therefore, nicotine can also be described as an alkaloid derived from aspartic acid. On the other hand, the pyrroHdine ring is biosynthesized from ornithine.When DL-[5- C]-pyrroline-5-carboxyhc acid, a postulated biosynthetic precursor derived from ornithine, was incorporated into Nicotiana mstica, the incorporated rate (0.04%) was very low, and the 2 - and 5 -positions were equally labeled with (F ure). Consequently, it was estimated that the biosynthetic intermediate was not this compound but another symmetrical structure [5]. 

Fodor (1976) has prepared a review of biosynthesis of tropane alkaloids for publication in Specialist Periodical Reports of the Chemical Society of London and, although it is too early to say for certain, some of the biosynthetic intermediates may be similar to the biodegradation intermediates. 

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