Biosynthesis and Elongation of Short- and Medium-Chain-Length Fatty Acids

Abstract

Short-and medium-chain-length fatty acids (FAs) are important constituents of a wide array of natural products. Branched and straight short-chain-length FAs originate from branched chain amino acid metabolism, and serve as primers for elongation in FA synthase-like reactions. However, a recent model proposes that the one-carbon extension reactions that utilize 2-oxo-3-methylbutyric acid in leucine biosynthesis also catalyze a repetitive one-carbon elongation of short-chain primers to medium-chain-length FAs. The existence of such a mechanism would require a novel form of regulation to control carbon flux between amino acid and FA biosynthesis. A critical re-analysis of the data used to support this pathway fails to support the hypothesis for FA elongation by onecarbon extension cycles of ␣-ketoacids. Therefore, we tested the hypothesis experimentally using criteria that distinguish between one-and two-carbon elongation mechanisms: (a) isotopomer patterns in terminal carbon atom pairs of branched and straight FAs resulting from differential labeling with The broad structural diversity of short-and mediumchain length fatty acids (scFAs and mcFAs, respectively) and their derivatives is incorporated into a wide array of biomolecules as components of antibiotics, insect pheromones, and plant storage lipids (Denoya et al., 1995;Laakel et al., 1994;Tang et al., 1994; Giblin-Davis et al., 1996;Schal et al., 1994;Pennanec' et al., 1991; Charlton and Roeloffs 1991;Knapp et al., 1991;Thompson et al., 1990; Hartman and Reimann, 1989). Understanding the biosynthesis of these compounds is critical both to understanding their regulation and designing strategies for their manipulation.scFAs and mcFAs are also found in sugar polyesters secreted by Solanaceous plants as defensive agents against a wide array of insect herbivores and pathogens (Gentile and Stoner, 1968; Gentile et al., 1968 Gentile et al., , 1969 Juvik et al., 1982 Juvik et al., , 1994 França et al., 1989). These polyesters are composed of either Glc or Suc to which as many as five or six FAs, respectively, may be esterified (Schumacher, 1970;Severson et al., 1985;King et al., 1986King et al., , 1990Shinozaki et al., 1991;Shapiro et al., 1994).The acyl substituents exhibit a remarkable degree of species-specific structural diversity: They range in length from 3:0 to 12:0, and include straight-chain, iso-branched, and anteiso-branched FAs with both odd and even numbers of carbon atoms.The biosynthesis of branched-chain FAs has been extensively investigated in bacteria (Oku and Kaneda, 1988;Kang et al., 1997aKang et al., , 1997bZelles, 1997). Iso-and anteisobranched FAs 14 to 17 carbon atoms long are derived from ␣-keto derivatives of Leu, Val, and Ile, which serve as short-chain primers for elongation. In this model, NAD ϩ -and CoA-dependent branched-chain ketoacid dehydrogenase provides acyl-CoA primers through oxidative decarboxylation of these ketoacid precursors. A FA synthase (FAS) system then elongates these three-to five-carbon primers utilizing malonyl...

Transcriptomic and Reverse Genetic Analysesof Branched-Chain Fatty Acid and Acyl Sugar Production inSolanum pennelliiandNicotiana benthamiana

“…In S. pennellii (and also later documented in Datura metel), short branched-chain acyl groups apparently act as primers for two-carbon elongation through the action of the FAS complex (Fig. 1A), a model that is supported by isotopic labeling studies (van der Hoeven and Steffens, 2000;Kroumova and Wagner, 2003). Contrasting with tomato and Datura, several tobacco species (including N. benthamiana) and Petunia species were shown by similar methodology to produce extended BCFAs (and also SCFAs in Petunia) via a one-carbon mechanism termed a-keto acid elongation (a-KAE; Fig.…”

“…1; Walters and Steffens, 1990). Historically, two alternative mechanisms were put forward in these and later studies for the elongation of BCFAs (and SCFAs) destined for sugar esters in the Solanaceae (Kroumova et al, 1994;van der Hoeven and Steffens, 2000). Interestingly, evidence now suggests that different species within this family utilize Figure 1.…”

Enzymatic synthesis of medium‐chain triacylglycerols by alcoholysis and interesterification of copra oil using a crude papain lipase preparation

“…Medium-chain fatty acids (MCFA), from caproic acid (C 6 ) to capric acid (C 10 ), have a strong potential in terms of energy, due to their digestibility, absorption and metabolism [1]. Triacylglycerols (TAG) containing a high content of MCFA are quickly solubilized, oxidized and metabolized upon digestion.…”

A Dynamic Interface for Capsaicinoid Systems Biology

“…in two-carbon increments derived from acetyl-CoA via the fatty acid synthase (Walters and Steffens, 1990;van der Hoeven and Steffens, 2000;Markai et al, 2002;Aluru et al, 2003;Slocombe et al, 2008).…”