Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb 21:6:172.
doi: 10.12688/f1000research.10466.1. eCollection 2017.

New insights into bacterial type II polyketide biosynthesis

Zhuan Zhang  1 , Hai-Xue Pan  1 , Gong-Li Tang  1
Affiliations
Review

New insights into bacterial type II polyketide biosynthesis

Zhuan Zhang et al. F1000Res. .

Abstract

Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984-1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013-2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included.

Keywords: PSKs; Type II polyketide biosynthesis; bacterial polyketide biosynthesis; type II polyketide synthases.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Non-acetate starter units involved in the biosynthesis of aurachins, trioxacarcins, and lomaiviticin A.
Figure 2.
Figure 2.. Advances in bacterial aromatic polyketide core biosynthesis.
( A) Regiospecific cyclizations catalyzed by aromatases (AROs)/cyclases (CYCs) TcmN, WhiE, ZhuI, StfQ, and BexL. ( B) SsfL2 catalyzes the fourth ring cyclization in tetracycline biosynthesis. KR, ketoreductase.
Figure 3.
Figure 3.. Progress in tailoring reactions catalyzed by flavin enzymes in the type II polyketide synthase system.
( A) Oxidative Favorskii-type rearrangement catalyzed by EncM in enterocin biosynthesis. ( B) XanO4 catalyzes epoxidation and Baeyer-Villiger (BV) dual reaction during the biosynthesis of xantholipin. ( C) Hydroxylation catalyzed by OxyS and reduction mediated by OxyR in the oxytetracycline pathway. ( D) B-ring contraction catalyzed by a conserved AIpJ/AIpK pair in kinamycin biosynthesis. ( E) MtmOIV catalyzes ring opening in mithramycin biosynthesis. ( F) BexE-mediated oxidative reactions during BE-7585A biosynthesis. FAD, flavin adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; SAM, S-adenosyl methionine.
Figure 4.
Figure 4.. Other enzymes for tailoring reactions in type II polyketide biosynthesis.
( A) P450-mediated intermolecular oxidative phenol coupling reaction. ( B) Divergent reactions catalyzed by non-heme iron enzymes SnoK and SnoN in the nogalamycin biosynthetic pathway. ( C) Epoxy hydrolases catalyzed by AIp1U and Lom6 in kinamycin and lomaiviticin biosynthesis. ( D) LanV and its homologous CabV (Urdmred)-catalyzed ketoreductions. ( E) ARX21-mediated keto-reductions. ( F) Reactions catalyzed by RdmB and DnrK. NADPH, reduced nicotinamide adenine dinucleotide phosphate; SAM, S-adenosyl methionine.
Figure 5.
Figure 5.. New developments in glycosylation and hybrid pathways for aromatic polyketide biosynthesis.
( A) AlnA/AlnB catalyzing C-ribosylation in alnumycin A biosynthesis. ( B) 2-Thiosugar biosynthesis in BE-7585A. ( C) Methyltransferase and glycosyltransferases in dutomycin biosynthesis. ( D) Convergent biosynthesis of simocyclinones. ( E) Type II polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid system in kosinostatin biosynthesis. ACP, acyl carrier protein; KS, ketosynthase.
Figure 6.
Figure 6.. Discovery of novel aromatic polyketides based on biosynthesis.
( A) 2-carboxamido-2-deacetyl-chelocardin (CDCHD) provided by biosynthetic engineering. ( B) Biosynthetic pathway of A-74528. ( C) Chartreusin analogues obtained by synthetic remodeling of the chartreusin pathway. ( D) Structures of chattamycin B, arenimycin , arimetamycin A, calixanthomycin A, and clostrubin A and B. ( E) Structures of jadomycin B, jadomycin Otc (1), and jadomycin 4-amino-L-phenylalanine. ( F) Non-enzymatic pyridine ring formation in rubrolones. PKS, polyketide synthase.
See this image and copyright information in PMC

References

    1. Das A, Khosla C: Biosynthesis of aromatic polyketides in bacteria. Acc Chem Res. 2009;42(5):631–9. 10.1021/ar8002249 - DOI - PMC - PubMed
    1. Zhou H, Li Y, Tang Y: Cyclization of aromatic polyketides from bacteria and fungi. Nat Prod Rep. 2010;27(6):839–68. 10.1039/b911518h - DOI - PMC - PubMed
    1. Hertweck C: The biosynthetic logic of polyketide diversity. Angew Chem Int Ed Engl. 2009;48(26):4688–716. 10.1002/anie.200806121 - DOI - PubMed
    1. Waldman AJ, Balskus EP: Lomaiviticin biosynthesis employs a new strategy for starter unit generation. Org Lett. 2014;16(2):640–3. 10.1021/ol403714g - DOI - PMC - PubMed
    1. Zhang M, Hou X, Qi L, et al. : Biosynthesis of trioxacarcin revealing a different starter unit and complex tailoring steps for type II polyketide synthase. Chem Sci. 2015;6:3440–7. 10.1039/C5SC00116A - DOI - PMC - PubMed

LinkOut - more resources