Starter Unit

Most of the type II PKSs studied so far used acetate as a starter unit. The minimal PKS appears to have intrinsic starter unit specificity for acetyl CoA, which could also be derived by decarboxylation from malonyl CoA, at least in vitro [173,183, 184]. Little is known about how a type II PKS chooses a starter imit other than acetate. The biosynthesis of 13 and 14 in S. peucetius and Streptomyces sp. C5, and oxytetracycline in Streptomyces rimosus are known examples in which a type II PKS used propionyl CoA [84,153,163] and malonamyl CoA [152] as a starter unit, respectively. However, engineered PKSs consisting of the KSa/KSp pair from either the dps [163] or otc [152] cluster produced poiyketides exclusively with an acetate starter, reinforcing the notion that the minimal PKS has an intrinsic specificity for an acetate starter. At least for the biosynthesis of 13 and 14 the choice of the propionate starter unit has been shown to depend on dedicated subunits, in addition to the minimal dps PKS, and on the protein/protein interactions among all the subunits of the resulting PKS complex [84,153,163]. 

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To make the whole starting sequence atitomaiic in a contactor type automatic starter unit it is essential to know the time the motor will take to accelerate from one slip to another between each step. It is required to select... 

Since it is not practical to manufacture a llameproof enclosure due to its size and bulk and the number of knockouts and openings on the doors for switches, metering, indicators, and pushbuttons (PBs) etc., it is common practice to locate the.se assemblies some distance from the affected area in a separate well-ventilated room. Depending upon the location and intensity ol contamination, it may be permissible to meet the requirement by using a pressurized enclosure by maintaining a positive pressure inside the enclosure similar to that for motors (Section 7.1.3..3). When there arc many switchgear assemblies, the room itself can be pressurized, which is safer and easier. Small enclosures, however, such as a PB station, switch or a switch fuse unit or an individual starter unit etc., which can be easily made of MS plates or cast iron, as discussed in Section 7.13, can be mounted in the hazardous area while the main MCC can be installed in the control room, away from the contaminated area and from where the process can be monitored. 

Xie and Dixon [27] underlined that although some models of proanthocyanidin biosynthesis show the extension units arising from condensation of an leucoanthocyanidin-derived electrophile with the nucleophilic 8 or 6 position of the starter unit, this scheme fails because of stereochemistry of leucoanthocyanidin is most likely 2,3-trans, whereas, in many cases, the extension units are 2,3-cis. One possible solution for this stereochemical para-... 

Long, P.F., Wilkinson, C.J., Bisang, C.P. et al. (2002) Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase. Molecular Microbiology, 43, 1215. 

The biosynthesis of polyketides (including chain initiation, elongation, and termination processes) is catalyzed by large multi-enzyme complexes called polyketide synthases (PKSs). The polyketides are synthesized from starter units such as acetyl-CoA, propionyl-CoA, and other acyl-CoA units. Extender units such as malonyl-CoA and methylmalonyl-CoA are repetitively added via a decarboxylative process to a growing carbon chain. Ultimately, the polyketide chain is released from the PKS by cleavage of the thioester, usually accompanied by chain cyclization [49]. 

PK synthases, alternatively, have significantly more regulated biosyntheses with regard to monomer choice. In most cases, elongation monomers are restricted to malonate and methylmalonate starter units. The major source of variability within these synthases lies in... 

Moore, B.S. and Hertweck, C. (2002) Biosynthesis and attachment of novel bacterial polyketide synthase starter units. Natural Product Reports, 19 (1), 70-99. 

L, loading module DH, dehydratase KS, p-ketosynthase KR, ketoreductase MT methyltransferase PS, pyran synthase DHh and KRh are DH and KR-like sequences, together with the FkbH domain, they are involved in the formation of D-lactate starter unit HMG-CS, hydroxy-methyl-glutaryl CoA synthase. Acyl-carrier-protein domains are shown as small filled balls with chain attached by the thiol group. The box shows the HMG-CS pathway for the formation of exocyclic enoate. 

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

The other acetogenins, shown in Table II, are a varied assortment of small molecule compounds which as a group contain alkene, alcohol, and carbonyl (acid, ester, aldehyde, and ketone) functionality. They are fairly typical substances with common structural features. Again, those compounds possessing an odd number of carbon atoms are less common, and biogenetlcally may be derived from a propionate starter unit. 

Formation and Modification of the Pseudodisaccharidic Core Unit. The characteristic design of the biosynthetic pathway for the FOR/IST- or 1,4-aminocyclitol-type AGAs is that it is mainly devoted to the formation and modification of a paromamine-related pseudodisaccharide. Hence, when the monoami-nocyclitol starter units are provided as sketched above, a glycosyltransfer reaction (fifth step) catalyzes by use of an M -type glycosyltransferase (ForM/lstM)... 

Figure 3.6. Polyketlde chains use an iterative process akin to the fatty acid chain elongation process. However, an extra layer of chemical diversity can be generated by feeding different starter units into the system consequently, the polyketlde biosynthetic system has been compared to a Lego system where a few modules can be joined together in many different ways.

In similar fashions, the core pathway up to C25 compounds (five isoprene units) is formed by sequential addition of C5 moieties derived from IPP to a starter unit derived from DMAPP. Thus, sesquiterpenes are formed form the precursor 2E, hS-farnesyl pyrophosphate (FPP), and diterpenes from 2E, 6E, IO -geranylgeranyl pyrophosphate (GGPP). The parents of triterpenes and tetraterpenes are formed by reductive coupling of two FPPs or GGPPs, respectively. Rubbers and other polyisoprenoids are produced from repeated additions of C5 units to the starter unit GGPP. 

Thus, combination of one acetate starter unit with seven malonates would give the Ci6 fatty acid, palmitic acid, and with eight malonates the Ci8 fatty acid, stearic acid. Note that the two carbons at the head of the chain (methyl end) are provided by acetate, not malonate, whilst the remainder are derived from malonate, which itself... 

Anthranilic acid (2-aminobenzoic acid) (see page 126) is another shikimate-derived compound which, as its CoA ester anthraniloyl-CoA, can act as a starter unit for malonate chain extension. Aromatization of the acetate-derived portion then leads to quinoline or acridine alkaloids, according to the number of acetate units incorporated (Figure 3.47). These products are similarly discussed elsewhere, under alkaloids (Chapter 6, page 376). 

Hexanoate is also likely to feature as a starter unit in the formation of the cannabinoids, a group of terpenophenolics found in Indian hemp (Cannabis sativa Cannabaceae). This plant, and preparations from it, known under a variety of names including hashish, marihuana, pot, bhang, charas, and dagga, have been used for centuries for the pleasurable sensations and mild euphoria experienced after its consumption, usually by smoking. 

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