title: Aminobenzoates as building blocks for natural product assembly lines.
abstract: The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3-aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3-aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. christopher_walsh@hms.harvard.edu
authors: Christopher T
authors: CT
authors: Walsh
authors: Stuart W
authors: SW
authors: Haynes
authors: Brian D
authors: BD
authors: Ames
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002827:Chorismic Acid / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000378:metabolism*; D062366:para-Aminobenzoates
chemical_list: D001688:Biological Products; D062367:ortho-Aminobenzoates; D062366:para-Aminobenzoates; D002827:Chorismic Acid; D010129:4-Aminobenzoic Acid