Biphenyl synthase

Benzophenone synthase (BPS) and biphenyl synthase (BIS) catalyze the formation of the same linear tetraketide from benzoyl-CoA and three molecules of malonyl-CoA. However, BPS cyclizes this intermediate via intramolecular C6-+C1 Claisen condensation, whereas BIS uses intramolecular C2— C7 aldol condensation. Benzophenone derivatives include polyprenylated polycyclic compounds with hi pharmaceutical potential. Biphenyl derivatives are the phytoalexins of the economically important Maloideae. 

Type III polyketide synthases (PKSs) generate a diverse array of natural products by condensing multiple acetyl units from malonyl-CoA to specific starter substrates (1,2). The homodimeric enzymes orchestrate a series of acyltransferase, decarboxylation, condensation, cyclization, and aromatizatidn reactions at two functionally independent active sites. Due to their ability to vary either the starter molecule or the type of cyclization and the number of condensations, they are, along with terpene synthases, one of the major generators of carbon skeleton diversity in plant secondary metabolites (i). Among the starter substrates used, benzoyl-CoA is a rare starter molecule. It is utilized by bacterial type I PKSs to form soraphen A, enterocin and the wailupemycins (4). in plants, benzoyl-CoA is the starter unit for two type III PKSs, benzophenone synthase (BPS) and biphenyl synthase (BIS), both of which were cloned in our laboratory. 

Figure 1. Type III polyketide synthases and their reaction products. CHS chalcone synthase, STS stilbene synthase BPS benzophenone synthase ACS acridone synthase VPS valerophenone synthase CTAS p-coumaryltriacetic acid synthase 2PS 2-pyrone synthase SPS styrylpyrone synthase BAS benzalacetone synthase H/EDS homoeryodyctiol/eriodyctiol chalcone synthase ALS Aloesone synthase PCS phertylchromone synthase BIS biphenyl synthase...

Figure 13.21 Mononuclear non-haem iron enzymes from each of the five families in structures which are poised for attack by 02. (a) The extradiol-cleaving catechol dioxygenase, 2,3-dihydroxy-biphenyl 1,2-dioxygenase (b) the Rieske dioxygenase, naphthalene 1,2-dioxygenase (c) isopenicillin N-synthase (d) the ot-ketoglutarate dependent enzyme clavaminate synthase and (e) the pterin-dependent phenylalanine hydroxylase. (From Koehntop et al., 2005. With kind permission of Springer Science and Business Media.)...

Asato, A.E., Peng, A., Hossain, M.Z., Mirzadegan, T., and Bertram, J.S., Azulenic retinoids. Novel nonbenzenoid aromatic retinoids with anticancer activity, 7. Med. Chem., 36, 3137, 1993. Hashizume, H., Ito, H., Kanaya, N., Nagashima, H., Usui, H., Oshima, R., Kanao, M., Tomoda, H., Sunazuka, T., Nagamitsu, T., Kumagai, H., and Omura, S., Synthesis and biological activities of new HMG-CoA synthase inhibitors. 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine. Heterocycles, 38, 1551, 1994. 

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