Biosynthetic genes

AGA (Complex, etc.) Compound Biosynthetic Genes Biosynthetic Proteins... 

A number of the genes involved in the biosynthesis of thiamine in E. coli (89—92), i hium meliloti (93), B. suhtilis (94), and Schi saccharomycespomhe (95,96) have been mapped, cloned, sequenced, and associated with biosynthetic functions. Thiamine biosynthesis is tightly controlled by feedback and repression mechanisms limiting overproduction (97,98). A cost-effective bioprocess for production of thiamine will require significant additional progress. 

The majority of industrial research describes classical approaches to yield improvement (49). However, there has been some work using genetically modified organisms. In the case of these recombinant organisms, the carotenoid biosynthetic gene cluster has been expressed in noncarotegenic species such as E. coli (50) and S. cerevisiae (51). 

The biosynthetic sequence for other aerobic bacteria appears, where known, to be similar to that in Pseudomonas dentrificans although the genes involved, and thus the enzymes, exhibit differences. 

Table 11.1 Predicted sizes and proposed functions of each protein product of the mitomycin C biosynthetic gene cluster.

There has been one report on the biosynthesis of FR900482 [114]. Radiolabeled D-glucosamine 33 and AHBA 38 were efficiently incorporated into 6, and D-[l-13C]-glucosamine was incorporated in the expected orientation (Figure 11.10). The biosynthetic gene cluster for FR900482 has been isolated from Streptomyces sandaensis and indicates a strong biosynthetic relationship with mitomycin C (Y. Mao, D. H. Sherman, unpublished results). 

A great deal has been learned about the biosynthesis of nitrogenases, but at the moment the process is understood only in broad outline. The detailed roles of the individual gene products require much further investigation, which may once more indicate fresh approaches to some of the problems identified herein. In particular, if the biosynthetic steps can be emulated chemically, then it may be possible to synthesize FeMoco in large quantities in order to allow its detailed analysis at the atomic level. 

In the biosynthetic approach, protein expression in E. coli [27], yeast [28, 29], and plants [30, 31] have been employed. This approach requires the construction of genes encoding for these repetitive polypeptides. Different methods for gene construction have been pubhshed multimerization [32], recursive directional ligation [33], and recursive directional ligation via plasmid reconstruction [23, 34]. 

Recent developments by academic and industrial geneticists may well prove to have transformed this situation. Tremendous progress has been made since the mid-1980s both in the isolation and manipulation ofthe biosynthetic genes in this pathway and in the related routes to the cephalosporins (via the cephalosporin C-producing... 

Elncidation of the Erwinia uredovora carotenoid biosynthetic pathway by functional analysis of gene prodncts expressed in Escherichia coif, J Bacteriol, 172, 6704-12. 

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